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Molecular Insight into Leukemia
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Molecular Insight into Leukemia

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 6565

Special Issue Editors

Dr. Claire Lucas

E-Mail Website
Guest Editor
1. Chester Medical School, University of Chester, Bache Hall, Chester CH2 1BR, UK
2. Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK
Interests: CML; blast crisis; clinical biomarkers; PP2A; CIP2A; AML
Dr. Ioannis Kanakis

E-Mail Website
Guest Editor
Chester Medical School, University of Chester, Bache Hall, Countess View, Chester CH2 1BR, UK
Interests: clinical biochemistry; bone metastases; musculoskeletal ageing
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Leukemias constitute a group of life-threatening malignant disorders of the blood and bone marrow. Over 500,000 patients are diagnosed with these conditions each year. Therefore, understanding the molecular bases underlying these diseases and developing biomarkers that control the occurrence of normal hematopoietic and leukemia will help us to develop more appropriate and effective treatment measures.

The aim of this Special Issue, entitled “Molecular Insight into Leukemia” is to provide an updated overview of the current knowledge of the pathogenesis and novel therapies of leukemias. Studies about the biological basis, new therapeutic strategies, treatment resistance, prognostic and diagnostic biomarkers of leukemias are welcomed.

Dr. Claire Lucas
Dr. Ioannis Kanakis
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • AML
  • CML
  • ALL
  • CLL
  • MLL
  • acute leukemia
  • chronic leukemia
  • myeloproliferative disorders
  • biomarkers
  • treatment
  • clinical outcome
  • treatment-free remission
  • bone marrow microenvironment

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Published Papers (3 papers)

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Research

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14 pages, 1784 KiB  
Article
The Role of PTEN in Chemoresistance Mediated by the HIF-1α/YY1 Axis in Pediatric Acute Lymphoblastic Leukemia
by Gabriela Antonio-Andres, Mario Morales-Martinez, Elva Jimenez-Hernandez and Sara Huerta-Yepez
Int. J. Mol. Sci. 2024, 25(14), 7767; https://doi.org/10.3390/ijms25147767 - 16 Jul 2024
Viewed by 913
Abstract
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current chemotherapy treatment regimens have improved survival rates to approximately 80%; however, resistance development remains the primary cause of treatment failure, affecting around 20% of cases. Some studies indicate that loss of the [...] Read more.
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current chemotherapy treatment regimens have improved survival rates to approximately 80%; however, resistance development remains the primary cause of treatment failure, affecting around 20% of cases. Some studies indicate that loss of the phosphatase and tensin homolog (PTEN) leads to deregulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, increasing the expression of proteins involved in chemoresistance. PTEN loss results in deregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces hypoxia-inducible factor 1-alpha (HIF-1α) expression in various cancers. Additionally, it triggers upregulation of the Yin Yang 1 (YY1) transcription factor, leading to chemoresistance mediated by glycoprotein p-170 (Gp-170). The aim of this study was to investigate the role of the PTEN/NF-κB axis in YY1 regulation via HIF-1α and its involvement in ALL. A PTEN inhibitor was administered in RS4;11 cells, followed by the evaluation of PTEN, NF-κB, HIF-1α, YY1, and Gp-170 expression, along with chemoresistance assessment. PTEN, HIF-1α, and YY1 expression levels were assessed in the peripheral blood mononuclear cells (PBMC) from pediatric ALL patients. The results reveal that the inhibition of PTEN activity significantly increases the expression of pAkt and NF-κB, which is consistent with the increase in the expression of HIF-1α and YY1 in RS4;11 cells. In turn, this inhibition increases the expression of the glycoprotein Gp-170, affecting doxorubicin accumulation in the cells treated with the inhibitor. Samples from pediatric ALL patients exhibit PTEN expression and higher HIF-1α and YY1 expression compared to controls. PTEN/Akt/NF-κB axis plays a critical role in the regulation of YY1 through HIF-1α, and this mechanism contributes to Gp-170-mediated chemoresistance in pediatric ALL. Full article
(This article belongs to the Special Issue Molecular Insight into Leukemia)
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12 pages, 1303 KiB  
Article
Application of Quantitative Structure-Activity Relationships in the Prediction of New Compounds with Anti-Leukemic Activity
by Cristian Sandoval, Francisco Torrens, Karina Godoy, Camila Reyes and Jorge Farías
Int. J. Mol. Sci. 2023, 24(15), 12258; https://doi.org/10.3390/ijms241512258 - 31 Jul 2023
Viewed by 1717
Abstract
Leukemia invades the bone marrow progressively and, through unknown mechanisms, outcompetes healthy hematopoiesis. Protein arginine methyltransferases 1 (PRMT1) are found in prokaryotes and eukaryotes cells. They are necessary for a number of biological processes and have been linked to several human diseases, including [...] Read more.
Leukemia invades the bone marrow progressively and, through unknown mechanisms, outcompetes healthy hematopoiesis. Protein arginine methyltransferases 1 (PRMT1) are found in prokaryotes and eukaryotes cells. They are necessary for a number of biological processes and have been linked to several human diseases, including cancer. Small compounds that target PRMT1 have a significant impact on both functional research and clinical disease treatment. In fact, numerous PRMT1 inhibitors targeting the S-adenosyl-L-methionine binding region have been studied. Through topographical descriptors, quantitative structure-activity relationships (QSAR) were developed in order to identify the most effective PRMT1 inhibitors among 17 compounds. The model built using linear discriminant analysis allows us to accurately classify over 90% of the investigated active substances. Antileukemic activity is predicted using a multilinear regression analysis, and it can account for more than 56% of the variation. Both analyses are validated using an internal “leave some out” test. The developed model could be utilized in future preclinical experiments with novel drugs. Full article
(This article belongs to the Special Issue Molecular Insight into Leukemia)
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Review

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26 pages, 774 KiB  
Review
Recent Updates in Venetoclax Combination Therapies in Pediatric Hematological Malignancies
by Maria Leśniak, Justyna Lipniarska, Patrycja Majka, Monika Lejman and Joanna Zawitkowska
Int. J. Mol. Sci. 2023, 24(23), 16708; https://doi.org/10.3390/ijms242316708 - 24 Nov 2023
Cited by 3 | Viewed by 3186
Abstract
Venetoclax is a strongly effective B-cell lymphoma-2 inhibitor (BCL-2) with an ability to selectively restore the apoptotic potential of cancerous cells. It has been proven that in combination with immunotherapy, targeted therapies, and lower-intensity therapies such as hypomethylating agents (HMAs) or low-dose cytarabine [...] Read more.
Venetoclax is a strongly effective B-cell lymphoma-2 inhibitor (BCL-2) with an ability to selectively restore the apoptotic potential of cancerous cells. It has been proven that in combination with immunotherapy, targeted therapies, and lower-intensity therapies such as hypomethylating agents (HMAs) or low-dose cytarabine (LDAC), the drug can improve overall outcomes for adult patients with acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), amongst other hematological malignancies, but its benefit in pediatric hematology remains unclear. With a number of preclinical and clinical trials emerging, the newest findings suggest that in many cases of younger patients, venetoclax combination treatment can be well-tolerated, with a safety profile similar to that in adults, despite often leading to severe infections. Studies aim to determine the activity of BCL-2 inhibitor in the treatment of both primary and refractory acute leukemias in combination with standard and high-dose chemotherapy. Although more research is required to identify the optimal venetoclax-based regimen for the pediatric population and its long-term effects on patients’ outcomes, it can become a potential therapeutic agent for pediatric oncology. Full article
(This article belongs to the Special Issue Molecular Insight into Leukemia)
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