Complex/variant translocations in chronic myelogenous leukemia (CML): genesis and prognosis with 4 new cases

Exp Mol Pathol. 2014 Aug;97(1):105-10. doi: 10.1016/j.yexmp.2014.06.004. Epub 2014 Jun 11.

Abstract

In 5-10% of cases with CML, variant or complex translocations (CT) are seen that may result in atypical fluorescence in situ hybridization signal patterns. Dual color, dual fusion fluorescence in situ hybridization (D-FISH) patterns are instrumental in identifying the genesis of these CT, but their prognostic implications remain controversial. The most common mechanism is a two-step process in which a standard two-way translocation (9;22) is followed by subsequent rearrangements involving other chromosomes. The second common mechanism is the one-step process wherein breakage occurs simultaneously on different chromosomes leading to CT. The typical D-FISH pattern seen with the one-step mechanism is 1F2G2R, while the pattern for the two-step mechanism can be variable (2F1G1R, 1F1G1R, 1F1G2R, 1F2G1R, etc.). We have studied 4 cases of CT using metaphase FISH with triple color, dual fusion ASS1, ABL1 and BCR probes to understand the genesis of these CT. All the patients were treated with imatinib, but only patients 3 and 4 showed remission. Our results indicate that the CT in cases 1, 3 and 4 arose from a one-step mechanism and case 2 from a multi-step mechanism. Response to imatinib varied from full remission to no response. Long term follow-up is necessary to evaluate the prognostic implications of these CT.

Keywords: BCR/ABL; CML; Complex rearrangement; D-FISH; Variant translocation.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Benzamides / therapeutic use
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Imatinib Mesylate
  • In Situ Hybridization, Fluorescence / methods
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Male
  • Middle Aged
  • Piperazines / therapeutic use
  • Prognosis
  • Pyrimidines / therapeutic use
  • Translocation, Genetic*

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl