Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms22126321
Keywords
hematologic malignancy; leukemia; lymphoma; myeloma; myelodysplastic syndrome; genetic; epigenetic; metabolic
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Hematologic malignancies are a diverse group of neoplasms arising from hematopoietic cells, commonly presenting as leukemias, lymphomas, and myelomas. Genetic analyses have revealed recurrent mutations that promote metabolic reprogramming and bidirectional communication between metabolites and the genome, shaping the cellular landscape during malignant hematopoiesis.
Hematologic malignancies comprise a heterogeneous group of neoplasms arising from hematopoietic cells or their precursors and most commonly presenting as leukemias, lymphomas, and myelomas. Genetic analyses have uncovered recurrent mutations which initiate or accumulate in the course of malignant transformation, as they provide selective growth advantage to the cell. These include mutations in genes encoding transcription factors and epigenetic regulators of metabolic genes, as well as genes encoding key metabolic enzymes. The resulting alterations contribute to the extensive metabolic reprogramming characterizing the transformed cell, supporting its increased biosynthetic needs and allowing it to withstand the metabolic stress that arises as a consequence of increased metabolic rates and changes in its microenvironment. Interestingly, this cross-talk is bidirectional, as metabolites also signal back to the nucleus and, via their widespread effects on modulating epigenetic modifications, shape the chromatin landscape and the transcriptional programs of the cell. In this article, we provide an overview of the main metabolic changes and relevant genetic alterations that characterize malignant hematopoiesis and discuss how, in turn, metabolites regulate epigenetic events during this process. The aim is to illustrate the intricate interrelationship between the genome (and epigenome) and metabolism and its relevance to hematologic malignancy.
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