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International Journal of Hematology
Published in: International Journal of Hematology 1/2017

01-07-2017 | Progress in Hematology

Epigenetic dysregulation of hematopoietic stem cells and preleukemic state

Authors: Hiroyoshi Kunimoto, Hideaki Nakajima

Published in: International Journal of Hematology | Issue 1/2017

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Abstract

Recent genetic analyses have revealed that premalignant somatic mutations in hematopoietic cells are common in older people without an evidence of hematologic malignancies, leading to clonal hematopoietic expansion. This phenomenon has been termed clonal hematopoiesis of indeterminate potential (CHIP). Frequency of such clonal somatic mutations increases with age: in 5–10% of people older than 70 years and around 20% of people older than 90 years. The most commonly mutated genes found in individuals with CHIP were epigenetic regulators, including DNA methyltransferase 3A (DNMT3A), Ten–eleven-translocation 2 (TET2), and Additional sex combs-like 1 (ASXL1), which are also recurrently mutated in myeloid malignancies. Recent functional studies have uncovered pleiotropic effect of mutations in DNMT3A, TET2, and ASXL1 in hematopoietic stem cell regulation and leukemic transformation. Of note, CHIP is associated with an increased risk of hematologic malignancy and all-cause mortality, albeit the annual risk of leukemic transformation was relatively low (0.5–1%). These findings suggest that clonal hematopoiesis per se may not be sufficient to engender preleukemic state. Further studies are required to decipher the exact mechanism by which preleukemic stem cells originate and transform into a full-blown leukemic state.
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Metadata
Title
Epigenetic dysregulation of hematopoietic stem cells and preleukemic state
Authors
Hiroyoshi Kunimoto
Hideaki Nakajima
Publication date
01-07-2017
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 1/2017
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2257-6

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