Aberrant DNA Methylation in Chronic Myeloid Leukemia: Cell Fate Control, Prognosis, and Therapeutic Response

Biochem Genet. 2018 Jun;56(3):149-175. doi: 10.1007/s10528-018-9841-1. Epub 2018 Jan 31.

Abstract

Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy characterized by the expression of the BCR-ABL1 fusion gene with different chimeric transcripts. Despite the crucial impact of constitutively active tyrosine kinase in CML pathogenesis, aberrant DNA methylation of certain genes plays an important role in disease progression and the development of drug resistance. This article reviews recent findings relevant to the effect of DNA methylation pattern of regulatory genes on various cellular activities such as cell proliferation and survival, as well as cell-signaling molecules in CML. These data might contribute to defining the role of aberrant DNA methylation in disease initiation and progression. However, further studies are needed on the validation of specific aberrant methylation markers regarding the prognosis and prediction of response among the CML patients.

Keywords: Apoptosis; Chronic myeloid leukemia; DNA methylation; Differentiation; Proliferation; Signaling Pathways.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Proliferation*
  • DNA Methylation*
  • DNA, Neoplasm* / genetics
  • DNA, Neoplasm* / metabolism
  • Disease-Free Survival
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / mortality
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm