Integration of amplified BCR/ABL fusion genes into the short arm of chromosome 17 as a novel mechanism of disease progression in chronic myeloid leukemia

Genes Chromosomes Cancer. 2001 May;31(1):10-4. doi: 10.1002/gcc.1112.

Abstract

We describe the cases of two patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML), in whom the extramedullary blastic phase developed during disease progression. The similar clinical presentations of these patients was accompanied by gain of identical secondary chromosome abnormalities, that is, monosomies 9, 14, and 22, and by a clustered amplification of the BCR/ABL fusion gene. The additional copies of the BCR/ABL fusion gene were integrated into the short arm of structurally abnormal chromosomes 17 in both patients. The conformity of these genetic features in two patients with a rare disease manifestation leads us to the assumption that either the clustered amplification of the BCR/ABL fusion gene or the integration of this cluster into the short arm of chromosome 17 or both are associated with extramedullar disease progression in CML. Furthermore, the insertion of amplified BCR/ABL fusion genes into structurally abnormal chromosomes provides a novel mechanism of disease progression in BCR/ABL-positive CML.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Blast Crisis / genetics
  • Blast Crisis / pathology
  • Chromosome Aberrations / genetics
  • Chromosome Aberrations / pathology
  • Chromosome Disorders
  • Chromosomes, Human, Pair 17 / genetics*
  • Cytogenetic Analysis
  • Disease Progression
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Amplification / genetics*
  • Genes, abl / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Fusion Proteins, bcr-abl