Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.2
2.8
Journals
Genes
Special Issues
Research Progress in Hematological Malignancies: A Molecular Genetics Perspective
share announcement

Research Progress in Hematological Malignancies: A Molecular Genetics Perspective

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (5 June 2024) | Viewed by 14313

Special Issue Editor

Dr. Rina Kansal

E-Mail Website
Guest Editor
Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA
Interests: hematopathology; molecular genetics; anatomic pathology; clinical pathology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Hematologic malignancies include myeloid, lymphoid, histiocytic, and dendritic cell lineage neoplasms and histiocytic and dendritic cell lineage. These neoplasms may clinically present acutely, such as in acute myeloid or lymphoblastic leukemias, or as a chronic condition, such as in myelodysplastic syndromes, myeloproliferative neoplasms, lymphomas, lymphoproliferative disorders, multiple myeloma, histiocytic, and dendritic cell neoplasms. Pre-malignant conditions, such as in situ lymphoid neoplasia, monoclonal B-cell lymphocytosis, precursor myeloid states, and monoclonal gammopathy of undetermined significance, and tumor-like proliferations that may mimic true malignant neoplasms are also recognized in the current 5th edition of the World Health Organization (WHO) classification of neoplasms of hematolymphoid tissues. Further, hematologic malignancies may be sporadic or inherited as a component of various constitutional genetic syndromes. Germline predisposition to hematologic malignancies is now increasingly recognized as an essential part of diagnosis for appropriate clinical management.

In the past two decades, significant strides in molecular genetics in hematologic malignancies have transformed our understanding of the pathogenesis of these neoplasms, leading to WHO classification updates and clinical implications for management, depending on precise diagnostic classification. Nevertheless, much is yet to be learned and applied for further progress in meaningful clinical advances for patients. In a few hematologic malignancies, novel immunotherapies and therapeutic agents targeting specific molecular genetic abnormalities are examples of precision medicine. This Special Issue welcomes original articles addressing any aspect(s) of the research progress in hematologic malignancies.

Dr. Rina Kansal
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Genes is an international peer-reviewed open access monthly 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 2600 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

  • leukemia
  • lymphoma
  • myeloma
  • histiocytic neoplasms
  • precursor neoplasms
  • genetic tumor syndromes
  • germline predisposition to malignancy
  • WHO classification
  • immunotherapy
  • precision medicine

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

9 pages, 241 KiB  
Article
New Genetic Markers of Skin T-Cell Lymphoma Treatment
by Vladimír Vašků, Petra Fialová and Anna Vašků
Genes 2024, 15(3), 358; https://doi.org/10.3390/genes15030358 - 13 Mar 2024
Viewed by 1557
Abstract
Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it [...] Read more.
Aim: Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147–CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3′UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells—macrophages, dendritic cells, and B cells. The aim of the study is to test genotype–phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. Materials and Methods: A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. Results: The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy—it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Conclusion: Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well. Full article
(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)
19 pages, 1537 KiB  
Article
Validation of Endogenous Control Genes by Real-Time Quantitative Reverse Transcriptase Polymerase Chain Reaction for Acute Leukemia Gene Expression Studies
by Flávia Melo Cunha de Pinho Pessoa, Vitória Beatriz de Jesus Viana, Marcelo Braga de Oliveira, Beatriz Maria Dias Nogueira, Rodrigo Monteiro Ribeiro, Deivide de Sousa Oliveira, Germison Silva Lopes, Ricardo Parente Garcia Vieira, Manoel Odorico de Moraes Filho, Maria Elisabete Amaral de Moraes, André Salim Khayat, Fabiano Cordeiro Moreira and Caroline Aquino Moreira-Nunes
Genes 2024, 15(2), 151; https://doi.org/10.3390/genes15020151 - 24 Jan 2024
Cited by 2 | Viewed by 2253
Abstract
Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute [...] Read more.
Reference genes are used as internal reaction controls for gene expression analysis, and for this reason, they are considered reliable and must meet several important criteria. In view of the absence of studies regarding the best reference gene for the analysis of acute leukemia patients, a panel of genes commonly used as endogenous controls was selected from the literature for stability analysis: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Abelson murine leukemia viral oncogene human homolog 1 (ABL), Hypoxanthine phosphoribosyl-transferase 1 (HPRT1), Ribosomal protein lateral stalk subunit P0 (RPLP0), β-actin (ACTB) and TATA box binding protein (TBP). The stability of candidate reference genes was analyzed according to three statistical methods of assessment, namely, NormFinder, GeNorm and R software (version 4.0.3). From this study’s analysis, it was possible to identify that the endogenous set composed of ACTB, ABL, TBP and RPLP0 demonstrated good performances and stable expressions between the analyzed groups. In addition to that, the GAPDH and HPRT genes could not be classified as good reference genes, considering that they presented a high standard deviation and great variability between groups, indicating low stability. Given these findings, this study suggests the main endogenous gene set for use as a control/reference for the gene expression in peripheral blood and bone marrow samples from patients with acute leukemias is composed of the ACTB, ABL, TBP and RPLP0 genes. Researchers may choose two to three of these housekeeping genes to perform data normalization. Full article
(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)
►▼ Show Figures

Figure 1

18 pages, 2207 KiB  
Article
A Comprehensive Metabolism-Related Gene Signature Predicts the Survival of Patients with Acute Myeloid Leukemia
by Yujia Zhai, Heng Shen and Hui Wei
Genes 2024, 15(1), 63; https://doi.org/10.3390/genes15010063 - 31 Dec 2023
Cited by 1 | Viewed by 1982
Abstract
(1) Background: Acute myeloid leukemia (AML) is a clonal malignancy with heterogeneity in genomics and clinical outcome. Metabolism reprogramming has been increasingly recognized to play an important role in the leukemogenesis and prognosis in AML. A comprehensive prognostic model based on metabolism signatures [...] Read more.
(1) Background: Acute myeloid leukemia (AML) is a clonal malignancy with heterogeneity in genomics and clinical outcome. Metabolism reprogramming has been increasingly recognized to play an important role in the leukemogenesis and prognosis in AML. A comprehensive prognostic model based on metabolism signatures has not yet been developed. (2) Methods: We applied Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) normalization to establish a metabolism-related prognostic gene signature based on glycolysis, fatty acid metabolism, and the tricarboxylic acid cycle gene signatures. The Cancer Genome Atlas-Acute Myeloid Leukemia-like (TCGA-LAML) cohort was set as the training dataset for model construction. Three independent AML cohorts (GSE37642, GSE10358, and GSE12417) combined from Gene Expression Omnibus (GEO) datasets and the Beat-AML dataset were retrieved as two validation sets to test the robustness of the model. The transcriptome data and clinic information of the cohorts were enrolled for the analysis. (3) Results: Divided by the median value of the metabolism risk score, the five-year overall survival (OS) of the high-risk and low-risk groups in the training set were 8.2% and 41.3% (p < 0.001), respectively. The five-year OS of the high-risk and low-risk groups in the combined GEO cohort were 25.5% and 37.3% (p = 0.002), respectively. In the Beat-AML cohort, the three-year OS of the high-risk and low-risk groups were 16.2% and 40.2% (p = 0.0035), respectively. The metabolism risk score showed a significantly negative association with the long-term survival of AML. Furthermore, this metabolism risk score was an independent unfavorable factor for OS by univariate analysis and multivariate analysis. (4) Conclusions: Our study constructed a comprehensive metabolism-related signature with twelve metabolism-related genes for the risk stratification and outcome prediction of AML. This novel signature might contribute to a better use of metabolism reprogramming factors as prognostic markers and provide novel insights into potential metabolism targets for AML treatment. Full article
(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)
►▼ Show Figures

Figure 1

Review

Jump to: Research

27 pages, 460 KiB  
Review
The CRISPR-Cas System and Clinical Applications of CRISPR-Based Gene Editing in Hematology with a Focus on Inherited Germline Predisposition to Hematologic Malignancies
by Rina Kansal
Genes 2024, 15(7), 863; https://doi.org/10.3390/genes15070863 - 1 Jul 2024
Cited by 1 | Viewed by 3468
Abstract
Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in [...] Read more.
Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing has begun to transform the treatment landscape of genetic diseases. The history of the discovery of CRISPR/CRISPR-associated (Cas) proteins/single-guide RNA (sgRNA)-based gene editing since the first report of repetitive sequences of unknown significance in 1987 is fascinating, highly instructive, and inspiring for future advances in medicine. The recent approval of CRISPR-Cas9-based gene therapy to treat patients with severe sickle cell anemia and transfusion-dependent β-thalassemia has renewed hope for treating other hematologic diseases, including patients with a germline predisposition to hematologic malignancies, who would benefit greatly from the development of CRISPR-inspired gene therapies. The purpose of this paper is three-fold: first, a chronological description of the history of CRISPR-Cas9-sgRNA-based gene editing; second, a brief description of the current state of clinical research in hematologic diseases, including selected applications in treating hematologic diseases with CRISPR-based gene therapy, preceded by a brief description of the current tools being used in clinical genome editing; and third, a presentation of the current progress in gene therapies in inherited hematologic diseases and bone marrow failure syndromes, to hopefully stimulate efforts towards developing these therapies for patients with inherited bone marrow failure syndromes and other inherited conditions with a germline predisposition to hematologic malignancies. Full article
(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)
15 pages, 4439 KiB  
Review
Resisting the Resistance: Navigating BTK Mutations in Chronic Lymphocytic Leukemia (CLL)
by Alexandra Chirino, Skye Montoya, Anita Safronenka and Justin Taylor
Genes 2023, 14(12), 2182; https://doi.org/10.3390/genes14122182 - 6 Dec 2023
Cited by 12 | Viewed by 4197
Abstract
Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream [...] Read more.
Bruton’s tyrosine kinase (BTK) plays a key role in the B-cell receptor (BCR) signaling pathway and confers anti-apoptotic and proliferative properties to malignant B-cells in chronic lymphocytic leukemia (CLL). Small molecule BTK inhibitors were designed to bind BTK’s active site and block downstream signaling. These drugs have now been used in the treatment of thousands of patients with CLL, the most common form of leukemia in the western hemisphere. However, adverse effects of early generations of BTK inhibitors and resistance to treatment have led to the development of newer, more selective and non-covalent BTK inhibitors. As the use of these newer generation BTK inhibitors has increased, novel BTK resistance mutations have come to light. This review aims to discuss previously known and novel BTK mutations, their mechanisms of resistance, and their relationship with patient treatment. Also discussed here are future studies that are needed to investigate the underlying cause allowing these mutations to occur and how they incite resistance. New treatments on the horizon that attempt to maneuver around these resistance mutations can be met with new resistance mutations, creating an unmet need for patients with CLL. Novel therapies and combinations that address all forms of resistance are discussed. Full article
(This article belongs to the Special Issue Research Progress in Hematological Malignancies: A Molecular Genetics Perspective)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop