Role of hypoxia factors in the transcriptional mechanisms of clonal hematopoiesis in myelodysplastic syndrome
https://doi.org/10.34215/1609-1175-2025-3-11-20
Abstract
The hypoxia-inducible factor (HIF) is a key regulator of the cellular response to hypoxia. This factor coordinates adaptation through the activation of genes controlling angiogenesis (VEGF), glucose metabolism (GLUT1, GLUT3), proliferation (IGF-2), pH homeostasis (CA IX), and erythropoiesis (EPO). Although the role of HIF as a marker of hypoxia and a driver of aggressiveness in solid tumors is well-established, its contribution to the pathogenesis of hematological diseases, particularly in the development of clonal hematopoiesis and leukemogenesis, remains poorly understood and controversial. In this literature review, we focus on analyzing the relationship between HIF-1α expression (the most studied isoform) and the disease severity of myelodysplastic syndrome (MDS), the risk of clonal hematopoiesis, and subsequent transformation to acute myeloid leukemia (AML). Special attention is given to the potential mechanisms by which hypoxia and HIF-1α may promote the selective advantage of the dysplastic clone (e.g., through alterations in metabolism, apoptosis, or interaction with the bone marrow stroma) and its malignant progression. The findings highlight the significance for MDS risk stratification and the search for novel therapeutic targets.
About the Authors
V. A. Nevzorova
Pacific State Medical University;
Regional Clinical Hospital No 2
Russian Federation
Russian Federation
Vladivostok
A. S. Volosatov
Pacific State Medical University;
Regional Clinical Hospital No 2
Russian Federation
Russian Federation
Alexey S. Volosatov, trainee physician of Hematology Department; Resident at the Institute of Therapy and Instrumental Diagnostics
55 Russkaya st., Vladivostok, 690105, Russia
2 Ostryakova ave., Vladivostok, 690002, Russia
A. V. Talko
Pacific State Medical University;
Regional Clinical Hospital No 2
Russian Federation
Russian Federation
Vladivostok
N. S. Muzychenko
Regional Clinical Hospital No 2
Russian Federation
Russian Federation
Vladivostok
V. S. Dubov
Regional Clinical Hospital No 2
Russian Federation
Russian Federation
Vladivostok
V. M. Chertok
Pacific State Medical University
Russian Federation
Russian Federation
Vladivostok
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Review
For citations:
Nevzorova V.A., Volosatov A.S., Talko A.V., Muzychenko N.S., Dubov V.S., Chertok V.M. Role of hypoxia factors in the transcriptional mechanisms of clonal hematopoiesis in myelodysplastic syndrome. Pacific Medical Journal. 2025;(3):11-20. (In Russ.) https://doi.org/10.34215/1609-1175-2025-3-11-20
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