Atypical patterns of BCR/ABL gene rearrangements by interphase fluorescence in situ hybridization (FISH) in patients with chronic myeloid leukemia

Fluorescent in situ hybridization (FISH) technique is increasingly used for the identification of BCR/ABL gene rearrangements in chronic myeloid leukemia (CML).Patients and Methods: Both typical and atypical pattern of BCR/ABL gene rearrangenzents was determined in 83 patients with CML referred to Fundeni Clinical Institute using dual fusion fluorescence in situ hybridization (DF-FISH) probes and conventional cytogenetics.Results: in the majority of cases - 82 out of 83- CML patients exhibited a translocation between chromosome 9 and 22, resulting in a Philadelphia chromosome and one patient, negative for the Ph chromosome, presented cryptic BCR/ABL rearrangement. All samples were analyzed both by FISH and conventional cytogenetics. In 71 out of 83 cases the typical interphase FISH signal patterns of BCR/ABL gene rearrangements was identified one red signal, one green signal and two fusion signals (1R1G2F). The rest of I I patients presented an atypical interphase FISH pattern. Atypical patterns included: loss of terminal region of derivative chromosome 9 (five patients), loss of derivative chromosome 9 (del(9q)der) (three patients), isodicentric 22 derivative chromosome fused at terminal region of q arm (one patient), isoderivative chromosomes 22 (ider(22)t(9:22) (q34;q11)) (one patient) and supernumerary Philadelphia (one patient).Conclusion: FISH technique exhibited an advantage of being simple and still allowing the identification of cryptic BCR-ABL insertion or variant Ph. Another advantage of this technique is that it allows examination of interphase nuclei in cases were no metaphases could be obtained and atypical patterns may have clinical prognostic implication.