Deletion of any part of the BCR or ABL gene on the derivative chromosome 9 is a poor prognostic marker in chronic myelogenous leukemia

Cancer Genet Cytogenet. 2006 Apr 1;166(1):65-73. doi: 10.1016/j.cancergencyto.2005.08.028.

Abstract

To evaluate the prognostic significance of submicroscopic deletions of the ABL or BCR gene associated with t(9;22) in chronic myelogenous leukemia (CML), we investigated the incidence of an ABL or BCR deletion on derivative chromosome 9 using fluorescence in situ hybridization (FISH). FISH was performed using the LSI BCR/ABL dual-fusion translocation probe on bone marrow cells of 86 patients with CML. Of 86 patients, ABL deletion was detected in 13 (15.1%) patients and BCR deletion in 8 patients (9.3%). Patients with ABL deletion showed shorter event-free survival time (EFS) than those without ABL deletion (P = 0.020). Patients with BCR deletion showed significantly short overall survival time (OS; P = 0.039). Patients with ABL and/or BCR deletion (14/86 patients, 16.3%) showed significantly short OS and EFS (median OS, 43.0 months; median EFS, 40.0 months), compared to the patients without any BCR or ABL gene deletions (median OS, 94.0 months; median EFS, 90.0 months; P = 0.041 for OS, P = 0.008 for EFS). All the patients with BCR deletion, except for one, had a concomitant ABL deletion, suggesting that BCR deletion occurs in conjunction with ABL deletion. In patients with ABL deletion only, BCR/ABL rearrangement with b2a2 mRNA type tended to be more frequent than in patients without any deletion of the two genes (P = 0.073). Deletion of any of the BCR or ABL genes on derivative chromosome 9 was associated with both short OS and EFS. We conclude that deletion of not only the ABL gene, but also of the BCR gene, is a poor prognostic marker that indicates rapid disease progression in CML.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Bone Marrow / chemistry
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Child
  • Chromosomes, Human, Pair 9 / genetics*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Deletion*
  • Genes, abl / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Incidence
  • Korea / epidemiology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / diagnosis
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-bcr / genetics*
  • Survival Rate

Substances

  • Fusion Proteins, bcr-abl
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr