Unique secondary chromosomal abnormalities are frequently found in the chronic phase of chronic myeloid leukemia in southern Vietnam

Cancer Genet Cytogenet. 2006 Jul 1;168(1):59-68. doi: 10.1016/j.cancergencyto.2005.12.010.

Abstract

During the Vietnam War, southern Vietnam was exposed to a large amount of dioxin, a strong human carcinogen. Although we have observed much shorter survival in southern Vietnamese chronic myeloid leukemia (CML) patients, the cause remains to be clarified. Here, we report cytogenetic and molecular findings for 47 CML patients. Cytogenetically, the Philadelphia (Ph) chromosome was found in 44 patients (93.6%); of the remaining 3 patients with Ph-negative CML, 2 exhibited BCR/ABL transcripts but no BCR/ABL FISH fusion signals, suggesting the existence of two clones, with and without the BCR/ABL fusion gene. Surprisingly, in 17 patients (36.2%) (4 at diagnosis, 11 during chronic phase, and 2 in accelerated phase), we found several unique secondary chromosome abnormalities including trisomy 13, partial trisomy 13, and abnormalities of 1p, 3p, 6p, 7p, 10p, and 11p, which are different from the so-called additional chromosome abnormalities (extra Ph, +8, i(17q), +19, and +21) observed in blastic phase CML. FISH analysis revealed the Ph translocation with der(9) deletion in 11 patients (23.4%). Of these, 2 had two clones, with and without der(9) deletion, suggesting that der(9) deletion would occur in a subset of patients during disease progression. These observations point to preexisting genetic instability that induces various secondary chromosome abnormalities and multiple clones, resulting in shorter survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chromosome Aberrations*
  • Chromosomes, Human, Pair 13 / genetics
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Gene Deletion
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics
  • Male
  • Middle Aged
  • Philadelphia Chromosome
  • RNA, Messenger / analysis
  • Translocation, Genetic / genetics
  • Trisomy / genetics
  • Vietnam

Substances

  • RNA, Messenger
  • abl-bcr fusion protein, human
  • Fusion Proteins, bcr-abl