Clonal hematopoiesis in Philadelphia chromosome-negative bone marrow cells of chronic myeloid leukemia patients receiving dasatinib

Leuk Res. 2010 Jun;34(6):708-13. doi: 10.1016/j.leukres.2009.08.032. Epub 2009 Oct 4.

Abstract

A clonal cytogenetic abnormality was observed in Philadelphia chromosome-negative bone marrow cells of 6/27 chronic myeloid leukemia patients (+8 in 4, -7 in 1, and 20q- in 1) with dasatinib-induced remissions. The X-linked human androgen receptor gene assay demonstrated clonality in one additional patient. Single nucleotide polymorphism array analysis revealed somatic uniparental disomy involving chromosome 17(p12-pter) in another patient. The TP53 gene had a 5' splice site deletion of exon 6 that caused alternative splicing, frame shifting and introduction of a premature stop codon. After three years, no patient developed myelodysplastic syndrome or acute myeloid leukemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Base Sequence
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / pathology
  • Bone Marrow Cells / physiology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Clone Cells / drug effects
  • Clone Cells / metabolism
  • Clone Cells / pathology*
  • Cytogenetic Analysis
  • Dasatinib
  • Female
  • Follow-Up Studies
  • Genes, p53
  • Hematopoiesis / drug effects
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Humans
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / drug therapy*
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / pathology
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / physiopathology*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Philadelphia Chromosome
  • Pyrimidines / therapeutic use*
  • Thiazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Thiazoles
  • Dasatinib