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Lack of BCR/ABL reciprocal fusion in variant Philadelphia chromosome translocations: a use of double fusion signal FISH and spectral karyotyping

Leukemia volume 14, pages 1157–1160 (2000)Cite this article

Approximately 5–10% of chronic myeloid leukemia (CML) patients carry a variant Philadelphia (Ph) chromosome translocation in which the Ph chromosome is derived through rearrangements other than the classic t(9;22). The classic reciprocal (9;22) rearrangement results in translocation of the 3′ end of the c-ABL proto-oncogene (ABL) at 9q34 to the 5′ end of the breakpoint cluster region (BCR) gene at 22q11.2 producing the BCR/ABL hybrid gene on the derivative 22. Similarly the 3′ end of BCR is translocated to 9q34 downstream from the 5′ABL site, resulting in the reciprocal ABL/BCR fusion gene on the derivative 9.

It has been generally thought that patients with classic and variant Ph translocations have the same molecular changes and are clinically and hematologically identical.1 Variant Ph translocations involving several partner chromosomes seem to be more frequently associated with additional chromosomal abnormalities unrelated to the Ph formation.2 PCR and Southern blot methods are commonly used to detect BCR/ABL rearrangements. In addition a double fusion fluorescence in situ hybridization (D-FISH) BCR/ABL probe can be used to monitor residual disease in CML using interphase nuclei.3 The D-FISH probe also reveals the locations of 3′ ABL and 5′BCR as well as 5′ABL and 3′BCR on metaphase chromosomes. The identification of complex rearrangements has recently been greatly facilitated by the use of multicolor spectral karyotyping (SKY) that allows the simultaneous and differential color display of all human chromosomes.4 In this retrospective study, we have used G-banding, SKY and D-FISH metaphase analysis to determine the chromosomal locations of each BCR and ABL gene involved in 10 variant Ph rearrangements.

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Authors and Affiliations

  1. Toronto General Hospital, Toronto, Ontario, Canada

    VD Markovic, D Bouman, J Bayani, J Al-Maghrabi, S Kamel-Reid & JA Squire

  2. University Health Network, Toronto, Ontario, Canada

    VD Markovic, D Bouman, S Kamel-Reid & JA Squire

  3. Ontario Cancer Institute, Toronto, Ontario, Canada

    J Bayani, J Al-Maghrabi, S Kamel-Reid & JA Squire

  4. Princess Margaret Hospital, Toronto, Ontario, Canada

    J Bayani, J Al-Maghrabi, S Kamel-Reid & JA Squire

  5. Department of Laboratory Medicine and Pathology, Toronto, Ontario, Canada

    J Bayani, J Al-Maghrabi, S Kamel-Reid & JA Squire

  6. Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

    S Kamel-Reid & JA Squire

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  1. VD Markovic
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  2. D Bouman
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Markovic, V., Bouman, D., Bayani, J. et al. Lack of BCR/ABL reciprocal fusion in variant Philadelphia chromosome translocations: a use of double fusion signal FISH and spectral karyotyping. Leukemia 14, 1157–1160 (2000). https://doi.org/10.1038/sj.leu.2401718

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