Genetic and epigenetic factors interacting with clonal hematopoiesis resulting in chronic myelomonocytic leukemia

Ryan M. Carr, Mrinal M. Patnaik

Research output: Contribution to journalReview articlepeer-review


Purpose of reviewSince 2016, the WHO has recognized the significant phenotypic heterogeneity of chronic myelomonocytic leukemia (CMML) as a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap disease. Although sharing many somatic mutations with MDS and MPN, the purpose of this review is to put recent biological findings of CMML in the context of evolutionary theory, highlighting it as a distinct evolutionary trajectory occurring in the context of clonal hematopoiesis.Recent findingsClonal hematopoiesis of indeterminate potential (CHIP), with a mutational spectrum and prevalence correlated with age, has been defined. Enriched in DNMT3A, TET2, and ASXL1 mutations, clonal evolution can progress into various evolutionary trajectories including CMML. Impact of founder mutations (primarily TET2) on increased hematopoietic stem cell fitness has been well characterized. Epistatic interactions between mutations and epigenetic events have been explored, both in CMML and its pediatric counterpart juvenile myelomonocytic leukemia, including CMML transformation to acute myeloid leukemia. Together, these findings have contributed significantly toward CMML evolutionary dynamics.SummaryDespite relatively few 'driver' mutations in CMML, evolutionary development of chronic leukemia remains incompletely understood. Recent studies have shed light on the importance of studying epigenetic consequences of mutations and epistasis between key mutations to better understand clonal architecture and evolutionary dynamics.

Original languageEnglish (US)
Pages (from-to)2-10
Number of pages9
JournalCurrent opinion in hematology
Issue number1
StatePublished - Jan 1 2020


  • RAS
  • additional sex combs-like 1
  • chronic myelomonocytic leukemia
  • clonal hematopoiesis
  • juvenile myelomonocytic leukemia
  • ten-eleven-Translocation

ASJC Scopus subject areas

  • General Medicine


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