P53 involvement in clonal hematopoiesis of indeterminate potential

Sisi Chen, Yan Liu

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

Purpose of reviewClonal hematopoiesis of indeterminate potential (CHIP) increases with age and occurs when a single mutant hematopoietic stem cell (HSC) contributes to a significant clonal proportion of mature blood lineages. Somatic mutations in the TP53 gene, which encodes the tumor suppressor protein p53, rank in the top five among genes that were mutated in CHIP. This review focuses on mechanisms by which mutant p53 promotes CHIP progression and drives the pathogenesis of hematological malignancies, including myelodysplastic syndromes, and acute myeloid leukemia.Recent findingsTP53 was frequently mutated in individuals with CHIP. Although clinical studies suggest that expansion of HSCs with TP53 mutations predisposes the elderly to hematological neoplasms, there is a significant gap in knowledge regarding the mechanisms by which TP53 mutations promote HSC expansion. Recent findings suggest that several cellular stressors, including hematopoietic transplantation, genotoxic stress, and inflammation, promote the expansion of HSCs with TP53 mutations. Further, TP53 mutations identified in CHIP cooperate with genetic and/or epigenetic changes in leukemogenesis.SummaryTP53 mutations identified in CHIP are associated with increased risks of de novo and therapy-related hematological neoplasms. Thus, targeting mutant p53 and related pathways holds great potential in preventing CHIP progression and treating hematological malignancies.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalCurrent opinion in hematology
Volume26
Issue number4
DOIs
StatePublished - Jul 1 2019

Keywords

  • TP53
  • acute myeloid leukemia
  • age-related clonal hematopoiesis
  • clonal hematopoiesis of indeterminate potential
  • myelodysplastic syndromes
  • p53

ASJC Scopus subject areas

  • Hematology

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