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Cancers
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Innovations in Cancer Diagnostic Evaluation and Biomarker Detection
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Innovations in Cancer Diagnostic Evaluation and Biomarker Detection

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: closed (4 May 2023) | Viewed by 91892

Special Issue Editor

Prof. Dr. Joseph D. Khoury

E-Mail Website
Guest Editor
Division of Pathology/Lab Medicine, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: leukemia; lymphoma; cancer biomarkers

Special Issue Information

Dear Colleagues,

The pace of innovations in laboratory techniques for cancer diagnosis, biomarker detection, and disease monitoring has expanded significantly over the past decade. Such innovations currently permit an unprecedented level of nuance and depth in terms of disease classification and detection of therapy targets across the continuum of cancer care. Since laboratory innovations currently form the basis of risk stratification and therapy selection in a broad array of cancers, understanding their strengths and limitations has become critical for informed treatment decisions.

This Special Issue will be focused on novel technologies and laboratory approaches employed in the diagnosis and classification of cancer, as well as the detection of tissue- and blood-based biomarkers that inform treatment decisions. We welcome research papers as well as expert reviews that shed light on the state-of-the-art of this critical area underpinning cancer care today.

Prof. Dr. Joseph D. Khoury
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • biomarker
  • laboratory techniques
  • pathology
  • tissue

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Published Papers (24 papers)

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14 pages, 1925 KiB  
Article
Clinical and Histopathological Features of an Italian Monocentric Series of Primary Small Bowel T-Cell Lymphomas
by Marco Lucioni, Sara Fraticelli, Giovanni Santacroce, Arturo Bonometti, Nicola Aronico, Roberta Sciarra, Marco Vincenzo Lenti, Paola Ilaria Bianchi, Giuseppe Neri, Monica Feltri, Benedetto Neri, Giuseppina Ferrario, Roberta Riboni, Gino Roberto Corazza, Alessandro Vanoli, Luca Arcaini, Marco Paulli and Antonio Di Sabatino
Cancers 2023, 15(10), 2743; https://doi.org/10.3390/cancers15102743 - 13 May 2023
Cited by 7 | Viewed by 1706
Abstract
The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical–pathological profile of a series [...] Read more.
The gastrointestinal (GI) tract is the most common extranodal site of occurrence of non-Hodgkin lymphomas. Most GI lymphomas are of B-cell lineage, while T-cell lymphomas are less frequent. The aim of our retrospective study was to depict the clinical–pathological profile of a series of patients affected by intestinal T-cell lymphomas (ITCL) and possibly define hallmarks of these neoplasms. A total of 28 patients were included: 17 enteropathy-associated T-cell lymphomas (EATL), 5 monomorphic epitheliotropic T-cell lymphomas (MEITL), 3 indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (ITCLDGT), and 3 intestinal T-cell lymphomas not otherwise specified (ITCL-NOS). Celiac disease (CD) was diagnosed in around 70% of cases. Diagnosis of EATL showed a significant correlation with CD30 expression, whereas MEITL with angiotropism and CD56 positivity. ITCLDGT cases showed plasma cells infiltration. Peripheral lymphocytosis, the absence of a previous diagnosis of CD, an advanced Lugano clinical stage, and the histological subtype ITCL-NOS were significantly associated with worse survival at multivariate analysis. Our findings about the epidemiological, clinical, and histopathological features of ITCL were in line with the current knowledge. Reliable prognostic tools for these neoplasms are still lacking but according to our results lymphocytosis, diagnosis of CD, Lugano clinical stage, and histological subtype should be considered for patient stratification. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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18 pages, 5208 KiB  
Article
Syntaxin-6, a Reliable Biomarker for Predicting the Prognosis of Patients with Cancer and the Effectiveness of Immunotherapy
by Wenchao Li, Kuan Li, Hongfa Wei, Yu Sun, Yangjing Liao, Yuan Zou, Xiancong Chen, Cuncan Deng, Songyao Chen, Yulong He, Mingyu Huo and Changhua Zhang
Cancers 2023, 15(1), 27; https://doi.org/10.3390/cancers15010027 - 21 Dec 2022
Cited by 2 | Viewed by 2405
Abstract
Syntaxin-6 (STX6), a vesicular transport protein, is a direct target of the tumor suppressor gene P53, supporting cancer growth dependent on P53. However, STX6’s function in the tumor microenvironment has yet to be reported. In this research, we comprehensively explored the role of [...] Read more.
Syntaxin-6 (STX6), a vesicular transport protein, is a direct target of the tumor suppressor gene P53, supporting cancer growth dependent on P53. However, STX6’s function in the tumor microenvironment has yet to be reported. In this research, we comprehensively explored the role of the oncogene STX6 in pan-cancer by combining data from several databases, including the Cancer Genome Atlas, CPTAC, cBioPortal, and TIMER. Then, we verified the carcinogenic effect of STX6 in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) through a series of experiments in vitro and in vivo. Bioinformatics analysis demonstrated that STX6 is an oncogene for several cancers and is mainly involved in the cell cycle, epithelial–mesenchymal transition, oxidative phosphorylation, and tumor immune modulation, especially for tumor-associated fibroblasts (CAFs) and NKT cells. Additionally, a high level of STX6 could indicate patients’ resistance to immunotherapy. Our own data indicated that the STX6 level was upregulated in HCC and CRC. Knockdown of the STX6 levels could arrest the cell cycle and restrain cell proliferation, migration, and invasion. RNA-seq indicated that STX6 was significantly involved in pathways for cancer, such as the MAPK signal pathway. In a mouse model, knockdown of STX6 inhibited tumor growth and potentiated anti-PD-1 efficacy. In light of the essential roles STX6 plays in carcinogenesis and cancer immunology, it has the potential to be a predictive biomarker and a target for cancer immunotherapy. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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12 pages, 2226 KiB  
Article
Tri-Compartmental Restriction Spectrum Imaging Breast Model Distinguishes Malignant Lesions from Benign Lesions and Healthy Tissue on Diffusion-Weighted Imaging
by Alexandra H. Besser, Lauren K. Fang, Michelle W. Tong, Maren M. Sjaastad Andreassen, Haydee Ojeda-Fournier, Christopher C. Conlin, Stéphane Loubrie, Tyler M. Seibert, Michael E. Hahn, Joshua M. Kuperman, Anne M. Wallace, Anders M. Dale, Ana E. Rodríguez-Soto and Rebecca A. Rakow-Penner
Cancers 2022, 14(13), 3200; https://doi.org/10.3390/cancers14133200 - 30 Jun 2022
Cited by 5 | Viewed by 2065
Abstract
Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) [...] Read more.
Diffusion-weighted MRI (DW-MRI) offers a potential adjunct to dynamic contrast-enhanced MRI to discriminate benign from malignant breast lesions by yielding quantitative information about tissue microstructure. Multi-component modeling of the DW-MRI signal over an extended b-value range (up to 3000 s/mm2) theoretically isolates the slowly diffusing (restricted) water component in tissues. Previously, a three-component restriction spectrum imaging (RSI) model demonstrated the ability to distinguish malignant lesions from healthy breast tissue. We further evaluated the utility of this three-component model to differentiate malignant from benign lesions and healthy tissue in 12 patients with known malignancy and synchronous pathology-proven benign lesions. The signal contributions from three distinct diffusion compartments were measured to generate parametric maps corresponding to diffusivity on a voxel-wise basis. The three-component model discriminated malignant from benign and healthy tissue, particularly using the restricted diffusion C1 compartment and product of the restricted and intermediate diffusion compartments (C1 and C2). However, benign lesions and healthy tissue did not significantly differ in diffusion characteristics. Quantitative discrimination of these three tissue types (malignant, benign, and healthy) in non-pre-defined lesions may enhance the clinical utility of DW-MRI in reducing excessive biopsies and aiding in surveillance and surgical evaluation without repeated exposure to gadolinium contrast. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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28 pages, 7042 KiB  
Article
Prediction of Adrenocortical Carcinoma Relapse and Prognosis with a Set of Novel Multigene Panels
by Xiaozeng Lin, Yan Gu, Yingying Su, Ying Dong, Pierre Major, Anil Kapoor and Damu Tang
Cancers 2022, 14(11), 2805; https://doi.org/10.3390/cancers14112805 - 5 Jun 2022
Cited by 4 | Viewed by 2655
Abstract
Effective assessment of adrenocortical carcinoma (ACC) prognosis is critical in patient management. We report four novel and robust prognostic multigene panels. Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B predict ACC relapse at area under the curve (AUC) of 0.89, 0.79, 0.78, and 0.80, respectively, and [...] Read more.
Effective assessment of adrenocortical carcinoma (ACC) prognosis is critical in patient management. We report four novel and robust prognostic multigene panels. Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B predict ACC relapse at area under the curve (AUC) of 0.89, 0.79, 0.78, and 0.80, respectively, and fatality at AUC of 0.91, 0.88, 0.85, and 0.87, respectively. Among their 33 component genes, 31 are novel. They could be differentially expressed in ACCs from normal tissues, tumors with different severity (stages and lymph node metastasis), ACCs with TP53 mutations, and tumors with differentially expressed immune checkpoints (CTLA4, PD1, TGFBR1, and others). All panels correlate with reductions of ACC-associated CD8+ and/or NK cells. Furthermore, we provide the first evidence for the association of mesenchymal stem cells (MSCs) with ACC relapse (p = 2 × 10−6) and prognosis (p = 2 × 10−8). Sig27var25, SigIQvar8, SigCmbnvar5, and SigCmbn_B correlate with MSC (spearman r ≥ 0.53, p ≤ 1.38 × 10−5). Sig27var25 and SigIQvar8 were derived from a prostate cancer (PC) and clear cell renal cell carcinoma (ccRCC) multigene signature, respectively; SigCmbnvar5 and SigCmbn_B are combinations of both panels, revealing close relationships of ACC with PC and ccRCC. The origin of these four panels from PC and ccRCC favors their prognostic potential towards ACC. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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16 pages, 2963 KiB  
Article
Chronic Lymphocytic Leukemia Progression Diagnosis with Intrinsic Cellular Patterns via Unsupervised Clustering
by Pingjun Chen, Siba El Hussein, Fuyong Xing, Muhammad Aminu, Aparajith Kannapiran, John D. Hazle, L. Jeffrey Medeiros, Ignacio I. Wistuba, David Jaffray, Joseph D. Khoury and Jia Wu
Cancers 2022, 14(10), 2398; https://doi.org/10.3390/cancers14102398 - 13 May 2022
Cited by 7 | Viewed by 3184
Abstract
Identifying the progression of chronic lymphocytic leukemia (CLL) to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) has significant clinical implications as it prompts a major change in patient management. However, the differentiation between these disease phases may [...] Read more.
Identifying the progression of chronic lymphocytic leukemia (CLL) to accelerated CLL (aCLL) or transformation to diffuse large B-cell lymphoma (Richter transformation; RT) has significant clinical implications as it prompts a major change in patient management. However, the differentiation between these disease phases may be challenging in routine practice. Unsupervised learning has gained increased attention because of its substantial potential in data intrinsic pattern discovery. Here, we demonstrate that cellular feature engineering, identifying cellular phenotypes via unsupervised clustering, provides the most robust analytic performance in analyzing digitized pathology slides (accuracy = 0.925, AUC = 0.978) when compared to alternative approaches, such as mixed features, supervised features, unsupervised/mixed/supervised feature fusion and selection, as well as patch-based convolutional neural network (CNN) feature extraction. We further validate the reproducibility and robustness of unsupervised feature extraction via stability and repeated splitting analysis, supporting its utility as a diagnostic aid in identifying CLL patients with histologic evidence of disease progression. The outcome of this study serves as proof of principle using an unsupervised machine learning scheme to enhance the diagnostic accuracy of the heterogeneous histology patterns that pathologists might not easily see. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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14 pages, 1738 KiB  
Article
Identification of uPAR Variants Acting as ceRNAs in Leukaemia Cells
by Mariaevelina Alfieri, Anna Li Santi, Luigia Meo, Valentina Giudice, Carmine Selleri and Pia Ragno
Cancers 2022, 14(8), 1980; https://doi.org/10.3390/cancers14081980 - 14 Apr 2022
Cited by 1 | Viewed by 1698
Abstract
The 3′untranslated region (3′UTR) of the urokinase (uPA) receptor (uPAR) mRNA can act as a competitive endogenous RNA (ceRNA) in acute myeloid leukaemia (AML) cells, promoting the expression of pro-tumoral targets, including uPAR. Here, we identified three variants of uPAR mRNA containing the [...] Read more.
The 3′untranslated region (3′UTR) of the urokinase (uPA) receptor (uPAR) mRNA can act as a competitive endogenous RNA (ceRNA) in acute myeloid leukaemia (AML) cells, promoting the expression of pro-tumoral targets, including uPAR. Here, we identified three variants of uPAR mRNA containing the 3′UTR, in KG1 and U937 leukaemia cells expressing low and high uPAR levels, respectively. Identified variants lack exon 5 (uPAR Δ5) or exon 6 (uPAR Δ6) or part of exon 6, exon 7 and part of 3′UTR (uPAR Δ6/7). uPAR Δ5 and uPAR Δ6 transcript levels were higher in U937 cells compared to KG1 cells. Both uPAR variants were expressed also in AML blasts, at higher levels as compared to CD34 hematopoietic cells from healthy donors. The presence of the 3′UTR conferred high instability to the uPAR Δ5 variant transcript, preventing its translation in protein. Overexpression of the uPAR Δ5-3′UTR variant regulated the expression of some pro-tumoral factors previously reported to be regulated by the 3′UTR of uPAR and increased KG1 cell adhesion, migration and proliferation. These results demonstrate the expression of uPAR mRNA variants containing the 3′UTR in AML cells and the ceRNA activity and the biological effects of the uPAR Δ5-3′UTR variant. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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22 pages, 2475 KiB  
Article
Computer-Assisted Image Processing System for Early Assessment of Lung Nodule Malignancy
by Ahmed Shaffie, Ahmed Soliman, Amr Eledkawy, Victor van Berkel and Ayman El-Baz
Cancers 2022, 14(5), 1117; https://doi.org/10.3390/cancers14051117 - 22 Feb 2022
Cited by 10 | Viewed by 2740
Abstract
Lung cancer is one of the most dreadful cancers, and its detection in the early stage is very important and challenging. This manuscript proposes a new computer-aided diagnosis system for lung cancer diagnosis from chest computed tomography scans. The proposed system extracts two [...] Read more.
Lung cancer is one of the most dreadful cancers, and its detection in the early stage is very important and challenging. This manuscript proposes a new computer-aided diagnosis system for lung cancer diagnosis from chest computed tomography scans. The proposed system extracts two different kinds of features, namely, appearance features and shape features. For the appearance features, a Histogram of oriented gradients, a Multi-view analytical Local Binary Pattern, and a Markov Gibbs Random Field are developed to give a good description of the lung nodule texture, which is one of the main distinguishing characteristics between benign and malignant nodules. For the shape features, Multi-view Peripheral Sum Curvature Scale Space, Spherical Harmonics Expansion, and a group of some fundamental morphological features are implemented to describe the outer contour complexity of the nodules, which is main factor in lung nodule diagnosis. Each feature is fed into a stacked auto-encoder followed by a soft-max classifier to generate the initial malignancy probability. Finally, all these probabilities are combined together and fed to the last network to give the final diagnosis. The system is validated using 727 nodules which are subset from the Lung Image Database Consortium (LIDC) dataset. The system shows very high performance measures and achieves 92.55%, 91.70%, and 93.40% for the accuracy, sensitivity, and specificity, respectively. This high performance shows the ability of the system to distinguish between the malignant and benign nodules precisely. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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18 pages, 3173 KiB  
Article
Quantification and Phenotypic Characterization of Extracellular Vesicles from Patients with Acute Myeloid and B-Cell Lymphoblastic Leukemia
by Marijana Miljkovic-Licina, Nicolas Arraud, Aicha Dorra Zahra, Patricia Ropraz and Thomas Matthes
Cancers 2022, 14(1), 56; https://doi.org/10.3390/cancers14010056 - 23 Dec 2021
Cited by 7 | Viewed by 3278
Abstract
Extracellular vesicles (EVs) act in cell-to-cell communication, delivering cargo from donor to recipient cells and modulating their physiological condition. EVs secreted by leukemic blasts in patients with leukemia have been shown to influence the fate of recipient cells in the bone marrow microenvironment. [...] Read more.
Extracellular vesicles (EVs) act in cell-to-cell communication, delivering cargo from donor to recipient cells and modulating their physiological condition. EVs secreted by leukemic blasts in patients with leukemia have been shown to influence the fate of recipient cells in the bone marrow microenvironment. Methods to quantify and to characterize them phenotypically are therefore urgently needed to study their functional role in leukemia development and to evaluate their potential as targets for therapy. We have used cryo-electron microscopy to study morphology and size of leukemic EVs, and nanoparticle tracking analysis and fluorescence triggering flow cytometry to quantify EVs in platelet-free plasma from a small cohort of leukemia patients and healthy blood donors. Additional studies with a capture bead-based assay allowed us to establish phenotypic signatures of leukemic EVs from 17 AML and 3 B-ALL patients by evaluating the expression of 37 surface antigens. In addition to tetraspanins and lineage-specific markers we found several adhesion molecules (CD29, and CD146) to be highly expressed by EVs from B-ALL and several leukemic stem cell antigens (CD44, CD105, CD133, and SSEA-4) to be expressed by EVs from AML patients. Further improvements in analytical methods to study EVs are needed before potentially using them as biomarkers for leukemia prognosis and follow-up. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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18 pages, 1224 KiB  
Article
Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia
by Susanti Susanti, Satrio Wibowo, Gilang Akbariani, Naomi Yoshuantari, Didik Setyo Heriyanto, Asep Muhamad Ridwanuloh, Hariyatun Hariyatun, Adeodatus Yuda Handaya, Johan Kurnianda, Susanna Hilda Hutajulu and Mohammad Ilyas
Cancers 2021, 13(24), 6245; https://doi.org/10.3390/cancers13246245 - 13 Dec 2021
Cited by 7 | Viewed by 3679
Abstract
There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in [...] Read more.
There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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12 pages, 4894 KiB  
Article
Integrated Clinical Genotype-Phenotype Characteristics of Blastic Plasmacytoid Dendritic Cell Neoplasm
by C. Cameron Yin, Naveen Pemmaraju, M. James You, Shaoying Li, Jie Xu, Wei Wang, Zhenya Tang, Omar Alswailmi, Kapil N. Bhalla, Muzaffar H. Qazilbash, Marina Konopleva and Joseph D. Khoury
Cancers 2021, 13(23), 5888; https://doi.org/10.3390/cancers13235888 - 23 Nov 2021
Cited by 20 | Viewed by 3410
Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm derived from plasmacytoid dendritic cells. While advances in understanding the pathophysiology of the disease have been made, integrated systematic analyses of the spectrum of immunophenotypic and molecular alterations in real-world clinical cases [...] Read more.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive neoplasm derived from plasmacytoid dendritic cells. While advances in understanding the pathophysiology of the disease have been made, integrated systematic analyses of the spectrum of immunophenotypic and molecular alterations in real-world clinical cases remain limited. We performed mutation profiling of 50 BPDCN cases and assessed our findings in the context of disease immunophenotype, cytogenetics, and clinical characteristics. Patients included 42 men and 8 women, with a median age of 68 years (range, 14–84) at diagnosis. Forty-two (84%) patients had at least one mutation, and 23 (46%) patients had ≥3 mutations. The most common mutations involved TET2 and ASXL1, detected in 28 (56%) and 23 (46%) patients, respectively. Co-existing TET2 and ASXL1 mutations were present in 17 (34%) patients. Other recurrent mutations included ZRSR2 (16%), ETV6 (13%), DNMT3A (10%), NRAS (10%), IKZF1 (9%), SRSF2 (9%), IDH2 (8%), JAK2 (6%), KRAS (4%), NOTCH1 (4%), and TP53 (4%). We also identified mutations that have not been reported previously, including ETNK1, HNRNPK, HRAS, KDM6A, RAD21, SF3A1, and SH2B3. All patients received chemotherapy, and 20 patients additionally received stem cell transplantation. With a median follow-up of 10.5 months (range, 1–71), 21 patients achieved complete remission, 4 had persistent disease, and 24 died. Patients younger than 65 years had longer overall survival compared to those who were ≥65 years (p = 0.0022). Patients who had ≥3 mutations or mutations in the DNA methylation pathway genes had shorter overall survival (p = 0.0119 and p = 0.0126, respectively). Stem cell transplantation significantly prolonged overall survival regardless of mutation status. In conclusion, the majority of patients with BPDCN have somatic mutations involving epigenetic regulators and RNA splicing factors, in addition to ETV6 and IKZF1, which are also frequently mutated. Older age, multiple mutations, and mutations in the DNA methylation pathway are poor prognostic factors. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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17 pages, 4035 KiB  
Article
T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
by Ming Liang Oon, Jing Quan Lim, Bernett Lee, Sai Mun Leong, Gwyneth Shook-Ting Soon, Zi Wei Wong, Evelyn Huizi Lim, Zhenhua Li, Allen Eng Juh Yeoh, Shangying Chen, Kenneth Hon Kim Ban, Tae-Hoon Chung, Soo-Yong Tan, Shih-Sung Chuang, Seiichi Kato, Shigeo Nakamura, Emiko Takahashi, Yong-Howe Ho, Joseph D. Khoury, Rex K. H. Au-Yeung, Chee-Leong Cheng, Soon-Thye Lim, Wee-Joo Chng, Claudio Tripodo, Olaf Rotzschke, Choon Kiat Ong and Siok-Bian Ngadd Show full author list remove Hide full author list
Cancers 2021, 13(2), 340; https://doi.org/10.3390/cancers13020340 - 19 Jan 2021
Cited by 6 | Viewed by 5050
Abstract
T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to [...] Read more.
T-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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22 pages, 4884 KiB  
Article
Sequential Colocalization of ERa, PR, and AR Hormone Receptors Using Confocal Microscopy Enables New Insights into Normal Breast and Prostate Tissue and Cancers
by Miguel Chenlo, Elvin Aliyev, Joana S. Rodrigues, Paula Vieiro-Balo, Manuel N. Blanco Freire, José Manuel Cameselle-Teijeiro and Clara V. Alvarez
Cancers 2020, 12(12), 3591; https://doi.org/10.3390/cancers12123591 - 30 Nov 2020
Cited by 2 | Viewed by 2744
Abstract
Multiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used [...] Read more.
Multiplex immunohistochemistry (mIHC) use markers staining different cell populations applying widefield optical microscopy. Resolution is low not resolving subcellular co-localization. We sought to colocalize markers at subcellular level with antibodies validated for clinical diagnosis, including the single secondary antibody (combination of anti-rabbit/mouse-antibodies) used for diagnostic IHC with any primary antibody, and confocal microscopy. We explore colocalization in the nucleus (ColNu) of nuclear hormone receptors (ERa, PR, and AR) along with the baseline marker p63 in paired samples of breast and prostate tissues. We established ColNu mIHCF as a reliable technique easily implemented in a hospital setting. In ERa+ breast cancer, we identified different colocalization patterns (nuclear or cytoplasmatic) with PR and AR on the luminal epithelium. A triple-negative breast-cancer case expressed membrane-only ERa. A PR-only case was double positive PR/p63. In normal prostate, we identified an ERa+/p63+/AR-negative distinct population. All prostate cancer cases characteristically expressed ERa on the apical membrane of the AR+ epithelium. We confirmed this using ERa IHC and needle-core biopsies. ColNu mIHCF is feasible and already revealed a new marker for prostate cancer and identified sub-patterns in breast cancer. It could be useful for pathology as well as for functional studies in normal prostate and breast tissues. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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14 pages, 1110 KiB  
Article
Contrast-Enhanced Mammography for Screening Women after Breast Conserving Surgery
by Jill Gluskin, Carolina Rossi Saccarelli, Daly Avendano, Maria Adele Marino, Almir G. V. Bitencourt, Melissa Pilewskie, Varadan Sevilimedu, Janice S. Sung, Katja Pinker and Maxine S. Jochelson
Cancers 2020, 12(12), 3495; https://doi.org/10.3390/cancers12123495 - 24 Nov 2020
Cited by 22 | Viewed by 3434
Abstract
To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic [...] Read more.
To investigate the value of contrast-enhanced mammography (CEM) compared to full-field digital mammography (FFDM) in screening breast cancer patients after breast-conserving surgery (BCS), this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective, single-institution study included 971 CEM exams in 541 asymptomatic patients treated with BCS who underwent screening CEM between January 2013 and November 2018. Histopathology, or at least a one-year follow-up, was used as the standard of reference. Twenty-one of 541 patients (3.9%) were diagnosed with ipsi- or contralateral breast cancer: six (28.6%) cancers were seen with low-energy images (equivalent to FFDM), an additional nine (42.9%) cancers were detected only on iodine (contrast-enhanced) images, and six interval cancers were identified within 365 days of a negative screening CEM. Of the 10 ipsilateral cancers detected on CEM, four were detected on low-energy images (40%). Of the five contralateral cancers detected on CEM, two were detected on low-energy images (40%). Overall, the cancer detection rate (CDR) for CEM was 15.4/1000 (15/971), and the positive predictive value (PPV3) of the biopsies performed was 42.9% (15/35). For findings seen on low-energy images, with or without contrast, the CDR was 6.2/1000 (6/971), and the PPV3 of the biopsies performed was 37.5% (6/16). In the post-BCS screening setting, CEM has a higher CDR than FFDM. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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13 pages, 10285 KiB  
Article
Feasibility, Image Quality and Clinical Evaluation of Contrast-Enhanced Breast MRI Performed in a Supine Position Compared to the Standard Prone Position
by Alfonso Fausto, Annarita Fanizzi, Luca Volterrani, Francesco Giuseppe Mazzei, Claudio Calabrese, Donato Casella, Marco Marcasciano, Raffaella Massafra, Daniele La Forgia and Maria Antonietta Mazzei
Cancers 2020, 12(9), 2364; https://doi.org/10.3390/cancers12092364 - 21 Aug 2020
Cited by 14 | Viewed by 5452
Abstract
Background: To assess the feasibility, image quality and diagnostic value of contrast-enhanced breast magnetic resonance imaging (MRI) performed in a supine compared to a prone position. Methods: One hundred and fifty-one patients who had undergone a breast MRI in both the standard prone [...] Read more.
Background: To assess the feasibility, image quality and diagnostic value of contrast-enhanced breast magnetic resonance imaging (MRI) performed in a supine compared to a prone position. Methods: One hundred and fifty-one patients who had undergone a breast MRI in both the standard prone and supine position were evaluated retrospectively. Two 1.5 T MR scanners were used with the same image resolution, sequences and contrast medium in all examinations. The image quality and the number and dimensions of lesions were assessed by two expert radiologists in an independent and randomized fashion. Two different classification systems were used. Histopathology was the standard of reference. Results: Two hundred and forty MRIs from 120 patients were compared. The analysis revealed 134 MRIs with monofocal (U), 68 with multifocal (M) and 38 with multicentric (C) lesions. There was no difference between the image quality and number of lesions in the prone and supine examinations. A significant difference in the lesion extension was observed between the prone and supine position. No significant differences emerged in the classification of the lesions detected in the prone compared to the supine position. Conclusions: It is possible to perform breast MRI in a supine position with the same image quality, resolution and diagnostic value as in a prone position. In the prone position, the lesion dimensions are overestimated with a higher wash-in peak than in the supine position. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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14 pages, 1913 KiB  
Article
Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging
by Hagen Kulbe, Oliver Klein, Zhiyang Wu, Eliane T. Taube, Wanja Kassuhn, David Horst, Silvia Darb-Esfahani, Paul Jank, Salem Abobaker, Frauke Ringel, Andreas du Bois, Florian Heitz, Jalid Sehouli and Elena I. Braicu
Cancers 2020, 12(8), 2000; https://doi.org/10.3390/cancers12082000 - 22 Jul 2020
Cited by 12 | Viewed by 3657
Abstract
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently [...] Read more.
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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8 pages, 1583 KiB  
Communication
Gene Pair Correlation Coefficients in Sphingolipid Metabolic Pathway as a Potential Prognostic Biomarker for Breast Cancer
by Meena Kishore Sakharkar, Sarinder Kaur Dhillon, Saravana Babu Chidambaram, Musthafa Mohamed Essa and Jian Yang
Cancers 2020, 12(7), 1747; https://doi.org/10.3390/cancers12071747 - 1 Jul 2020
Cited by 9 | Viewed by 3746
Abstract
Complex diseases such as cancer are usually governed by dynamic and simultaneous modifications of multiple genes. Since sphingolipids are potent bioactive molecules and regulate many important pathophysiological processes such as carcinogenesis, we studied the gene pair correlations of 36 genes (31 genes in [...] Read more.
Complex diseases such as cancer are usually governed by dynamic and simultaneous modifications of multiple genes. Since sphingolipids are potent bioactive molecules and regulate many important pathophysiological processes such as carcinogenesis, we studied the gene pair correlations of 36 genes (31 genes in the sphingolipid metabolic pathway and 5 genes encoding the sphingosine-1-phosphate receptors) between breast cancer patients and healthy controls. It is remarkable to observe that the gene expressions were widely and strongly correlated in healthy controls but in general lost in breast cancer patients. This study suggests that gene pair correlation coefficients could be applied as a systematic and novel method for the diagnosis and prognosis of breast cancer. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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13 pages, 2429 KiB  
Communication
The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles
by Elise Aasebø, Frode S. Berven, Randi Hovland, Stein Ove Døskeland, Øystein Bruserud, Frode Selheim and Maria Hernandez-Valladares
Cancers 2020, 12(6), 1466; https://doi.org/10.3390/cancers12061466 - 4 Jun 2020
Cited by 34 | Viewed by 5102
Abstract
Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at [...] Read more.
Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping molecular mechanisms that contribute to this chemoresistance. We used liquid chromatography–tandem mass spectrometry (LC–MS/MS) to compare the proteomic and phosphoproteomic profiles of AML cells derived from seven patients at the time of first diagnosis and at first relapse. At the time of first relapse, AML cells were characterized by increased levels of proteins important for various mitochondrial functions, such as mitochondrial ribosomal subunit proteins (MRPL21, MRPS37) and proteins for RNA processing (DHX37, RNA helicase; RPP40, ribonuclease P component), DNA repair (ERCC3, DNA repair factor IIH helicase; GTF2F1, general transcription factor), and cyclin-dependent kinase (CDK) activity. The levels of several cytoskeletal proteins (MYH14/MYL6/MYL12A, myosin chains; VCL, vinculin) as well as of proteins involved in vesicular trafficking/secretion and cell adhesion (ITGAX, integrin alpha-X; CD36, platelet glycoprotein 4; SLC2A3, solute carrier family 2) were decreased in relapsed cells. Our study introduces new targetable proteins that might direct therapeutic strategies to decrease chemoresistance in relapsed AML. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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18 pages, 5564 KiB  
Article
Classification of Breast Cancer Cells Using the Integration of High-Frequency Single-Beam Acoustic Tweezers and Convolutional Neural Networks
by Hae Gyun Lim, O-Joun Lee, K. Kirk Shung, Jin-Taek Kim and Hyung Ham Kim
Cancers 2020, 12(5), 1212; https://doi.org/10.3390/cancers12051212 - 12 May 2020
Cited by 20 | Viewed by 3905
Abstract
Single-beam acoustic tweezers (SBAT) is a widely used trapping technique to manipulate microscopic particles or cells. Recently, the characterization of a single cancer cell using high-frequency (>30 MHz) SBAT has been reported to determine its invasiveness and metastatic potential. Investigation of cell elasticity [...] Read more.
Single-beam acoustic tweezers (SBAT) is a widely used trapping technique to manipulate microscopic particles or cells. Recently, the characterization of a single cancer cell using high-frequency (>30 MHz) SBAT has been reported to determine its invasiveness and metastatic potential. Investigation of cell elasticity and invasiveness is based on the deformability of cells under SBAT’s radiation forces, and in general, more physically deformed cells exhibit higher levels of invasiveness and therefore higher metastatic potential. However, previous imaging analysis to determine substantial differences in cell deformation, where the SBAT is turned ON or OFF, relies on the subjective observation that may vary and requires follow-up evaluations from experts. In this study, we propose an automatic and reliable cancer cell classification method based on SBAT and a convolutional neural network (CNN), which provides objective and accurate quantitative measurement results. We used a custom-designed 50 MHz SBAT transducer to obtain a series of images of deformed human breast cancer cells. CNN-based classification methods with data augmentation applied to collected images determined and validated the metastatic potential of cancer cells. As a result, with the selected optimizers, precision, and recall of the model were found to be greater than 0.95, which highly validates the classification performance of our integrated method. CNN-guided cancer cell deformation analysis using SBAT may be a promising alternative to current histological image analysis, and this pretrained model will significantly reduce the evaluation time for a larger population of cells. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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Graphical abstract

26 pages, 2326 KiB  
Article
Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia
by Elise Aasebø, Frode S. Berven, Sushma Bartaula-Brevik, Tomasz Stokowy, Randi Hovland, Marc Vaudel, Stein Ove Døskeland, Emmet McCormack, Tanveer S. Batth, Jesper V. Olsen, Øystein Bruserud, Frode Selheim and Maria Hernandez-Valladares
Cancers 2020, 12(3), 709; https://doi.org/10.3390/cancers12030709 - 17 Mar 2020
Cited by 35 | Viewed by 5999
Abstract
Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse [...] Read more.
Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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Review

Jump to: Research, Other

12 pages, 525 KiB  
Review
Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions
by Haneen T. Salah, Courtney D. DiNardo, Marina Konopleva and Joseph D. Khoury
Cancers 2021, 13(12), 2974; https://doi.org/10.3390/cancers13122974 - 14 Jun 2021
Cited by 13 | Viewed by 4204
Abstract
Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic [...] Read more.
Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic lymphoid leukemia and acute myeloid leukemia. Given the reported resistance to venetoclax, understanding the mechanisms of resistance and the potential biomarkers of response is crucial to ensure optimal drug usage and improved patient outcomes. Mechanisms of resistance to venetoclax include alterations involving the BH3-binding groove, BCL2 gene mutations affecting venetoclax binding, and activation of alternative anti-apoptotic pathways. Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and TP53 loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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21 pages, 3916 KiB  
Review
CD123 as a Biomarker in Hematolymphoid Malignancies: Principles of Detection and Targeted Therapies
by Hanadi El Achi, Edouard Dupont, Shilpa Paul and Joseph D. Khoury
Cancers 2020, 12(11), 3087; https://doi.org/10.3390/cancers12113087 - 23 Oct 2020
Cited by 28 | Viewed by 8204
Abstract
CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated [...] Read more.
CD123, the α chain of the interleukin 3 receptor, is a cytokine receptor that is overexpressed in multiple hematolymphoid neoplasms, including acute myeloid leukemia, blastic plasmacytoid dendritic cell neoplasm, acute lymphoblastic leukemia, hairy cell leukemia, and systemic mastocytosis. Importantly, CD123 expression is upregulated in leukemic stem cells relative to non-neoplastic hematopoietic stem cells, which makes it a useful diagnostic and therapeutic biomarker in hematologic malignancies. Varying levels of evidence have shown that CD123-targeted therapy represents a promising therapeutic approach in several cancers. Tagraxofusp, an anti-CD123 antibody conjugated to a diphtheria toxin, has been approved for use in patients with blastic plasmacytoid dendritic cell neoplasm. Multiple clinical trials are investigating the use of various CD123-targeting agents, including chimeric antigen receptor-modified T cells (expressing CD123, monoclonal antibodies, combined CD3-CD123 dual-affinity retargeting antibody therapy, recombinant fusion proteins, and CD123-engager T cells. In this review, we provide an overview of laboratory techniques used to evaluate and monitor CD123 expression, describe the strengths and limitations of detecting this biomarker in guiding therapy decisions, and provide an overview of the pharmacologic principles and strategies used in CD123-targeted therapies. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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15 pages, 799 KiB  
Review
Aggressive NK Cell Leukemia: Current State of the Art
by Siba El Hussein, L. Jeffrey Medeiros and Joseph D. Khoury
Cancers 2020, 12(10), 2900; https://doi.org/10.3390/cancers12102900 - 9 Oct 2020
Cited by 27 | Viewed by 5303
Abstract
Aggressive natural killer (NK) cell leukemia (ANKL) is a rare disease with a grave prognosis. Patients commonly present acutely with fever, constitutional symptoms, hepatosplenomegaly, and often disseminated intravascular coagulation or hemophagocytic syndrome. This acute clinical presentation and the variable pathologic and immunophenotypic features [...] Read more.
Aggressive natural killer (NK) cell leukemia (ANKL) is a rare disease with a grave prognosis. Patients commonly present acutely with fever, constitutional symptoms, hepatosplenomegaly, and often disseminated intravascular coagulation or hemophagocytic syndrome. This acute clinical presentation and the variable pathologic and immunophenotypic features of ANKL overlap with other diagnostic entities, making it challenging to establish a timely and accurate diagnosis of ANKL. Since its original recognition in 1986, substantial progress in understanding this disease using traditional pathologic approaches has improved diagnostic accuracy. This progress, in turn, has facilitated the performance of recent high-throughput studies that have yielded insights into pathogenesis. Molecular abnormalities that occur in ANKL can be divided into three major groups: JAK/STAT pathway activation, epigenetic dysregulation, and impairment of TP53 and DNA repair. These high-throughput data also have provided potential therapeutic targets that promise to improve therapy and outcomes for patients with ANKL. In this review, we provide a historical context of the conception and evolution of ANKL as a disease entity, we highlight advances in diagnostic criteria to recognize this disease, and we review recent understanding of pathogenesis as well as biomarker discoveries that are providing groundwork for innovative therapies. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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24 pages, 1573 KiB  
Review
The Role of Deubiquitinating Enzymes in Hematopoiesis and Hematological Malignancies
by Neha Sarodaya, Janardhan Karapurkar, Kye-Seong Kim, Seok-Ho Hong and Suresh Ramakrishna
Cancers 2020, 12(5), 1103; https://doi.org/10.3390/cancers12051103 - 28 Apr 2020
Cited by 14 | Viewed by 5000
Abstract
Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human lifespan. Single HSCs can give rise to at least eight distinct blood-cell lineages. Together, hematopoiesis, erythropoiesis, and angiogenesis coordinate several biological processes, i.e., cellular interactions during development and [...] Read more.
Hematopoietic stem cells (HSCs) are responsible for the production of blood cells throughout the human lifespan. Single HSCs can give rise to at least eight distinct blood-cell lineages. Together, hematopoiesis, erythropoiesis, and angiogenesis coordinate several biological processes, i.e., cellular interactions during development and proliferation, guided migration, lineage programming, and reprogramming by transcription factors. Any dysregulation of these processes can result in hematological disorders and/or malignancies. Several studies of the molecular mechanisms governing HSC maintenance have demonstrated that protein regulation by the ubiquitin proteasomal pathway is crucial for normal HSC function. Recent studies have shown that reversal of ubiquitination by deubiquitinating enzymes (DUBs) plays an equally important role in hematopoiesis; however, information regarding the biological function of DUBs is limited. In this review, we focus on recent discoveries about the physiological roles of DUBs in hematopoiesis, erythropoiesis, and angiogenesis and discuss the DUBs associated with common hematological disorders and malignancies, which are potential therapeutic drug targets. Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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Other

Jump to: Research, Review

2 pages, 160 KiB  
Comment
Comment on Aasebø, E., et al. “The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles”. Cancers 2020, 12, 1466
by Peter DeRosa and Victor Nava
Cancers 2020, 12(9), 2461; https://doi.org/10.3390/cancers12092461 - 31 Aug 2020
Cited by 2 | Viewed by 1553
Abstract
In a recent article published in this journal, Aasebø and colleagues reported [...] Full article
(This article belongs to the Special Issue Innovations in Cancer Diagnostic Evaluation and Biomarker Detection)
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