Clonal Hematopoiesis and therapy related MDS/AML

Best Pract Res Clin Haematol. 2019 Mar;32(1):13-23. doi: 10.1016/j.beha.2019.02.006. Epub 2019 Feb 15.

Abstract

Clonal Hematopoiesis is defined as the presence of mutations in peripheral blood in the absence of myeloid malignancies and is thought to occur as a normal part of ageing due to the fitness advantage conferred by these mutations in an ageing hematopoietic compartment. Therapy related myeloid neoplasms are malignancies that occur after exposure to chemotherapy/radiation and are associated with poor survival. Clonal hematopoiesis mutations represent a pre malignant state that can be triggered by exposure to cytotoxic damage and rapid hematopoietic stem cell expansion. We discuss in this review clinical evidence of association of clonal hematopoiesis with risk of therapy related myeloid neoplasms, the underlying mechanisms of clonal expansion under different cellular stresses and recommendations on clinical follow up of patients with clonal hematopoiesis including possible strategies for prevention of therapy related myeloid neoplasms.

Keywords: ARCH; CHIP; Clonal hematopoiesis; Therapy related MDS/AML; Therapy related myeloid neoplasm.

Publication types

  • Review

MeSH terms

  • Hematopoiesis / genetics*
  • Hematopoietic Stem Cells* / metabolism
  • Hematopoietic Stem Cells* / pathology
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / metabolism
  • Leukemia, Myeloid, Acute* / pathology
  • Leukemia, Myeloid, Acute* / therapy
  • Mutation*
  • Myelodysplastic Syndromes* / genetics
  • Myelodysplastic Syndromes* / metabolism
  • Myelodysplastic Syndromes* / therapy
  • Neoplasms, Second Primary* / genetics
  • Neoplasms, Second Primary* / metabolism
  • Neoplasms, Second Primary* / pathology
  • Neoplasms, Second Primary* / therapy