BCR/ABL rearrangement in two cases of Philadelphia chromosome negative chronic myeloid leukemia: deletion on the derivative chromosome 9 may or not be present

Cancer Genet Cytogenet. 2005 Dec;163(2):164-7. doi: 10.1016/j.cancergencyto.2005.04.021.

Abstract

The BCR/ABL gene rearrangement is the causing factor in chronic myeloid leukemia (CML). In most cases, it is cytogenetically visualized as a translocation between chromosomes 9 and 22, known as the Philadelphia (Ph) translocation. About 5-10% of CML patients lack cytogenetic evidence of the Ph translocation but show BCR/ABL fusion by fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction. Deletions around the breakpoints on the derivative 9 including ABL and or BCR sequences occur in 10-15% of Ph+ CML patients and are thought to have prognostic significance. We describe two patients with CML and normal karyotype in whom cryptic rearrangements involving chromosomes 9 and 22 resulted in the causative BCR/ABL gene. FISH with a three-color probe combination revealed BCR/ABL fusion on chromosome 9 without deletion in one patient; the other patient had BCR/ABL on chromosome 22 with an associated derivative 9 deletion. We discuss the proposed mechanisms in the formation of BCR/ABL in the setting of a normal karyotype. Some authors reported that patients with the chimeric gene located on the derivative 9 have a poor clinical course. We suggest that deletion rather than location of the chimeric gene alone is more likely to be associated with prognosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 22
  • Chromosomes, Human, Pair 9*
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Gene Rearrangement*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / genetics*
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Deletion*

Substances

  • Fusion Proteins, bcr-abl