Genetic and epigenetic heterogeneity and the impact on cancer relapse

Exp Hematol. 2017 Oct:54:26-30. doi: 10.1016/j.exphem.2017.07.002. Epub 2017 Jul 10.

Abstract

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with an exceedingly poor prognosis: a 5-year overall survival rate of 40%-45% in the young and a 5-year survival rate of less than 10% in the elderly (>60 years of age). Although a high percentage of patients enters complete remission after chemotherapeutic intervention, the majority of patients relapse within 3 years. Such stark prognostic outcomes highlight the need for additional clinical research, basic discovery, and molecular delineation of the etiologies and mechanisms behind responses to therapy that lead to relapse. Here, we summarize recent discoveries in tumor heterogeneity at the genetic and epigenetic levels and their independent molecular trajectories and dynamics in response to therapy. These new discoveries may have significant implications for understanding, monitoring, and treating leukemia and other cancers.

Publication types

  • Review
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antineoplastic Agents / therapeutic use
  • Chromosome Aberrations*
  • Drug Resistance, Neoplasm / genetics
  • Epigenesis, Genetic*
  • Gene Expression Regulation, Leukemic*
  • Genetic Heterogeneity*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Mutation
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Prognosis
  • Recurrence
  • Remission Induction
  • Single-Cell Analysis
  • Survival Analysis

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins