Variant Philadelphia chromosome identified by interphase fluorescence in situ hybridization (FISH) without evidence on G-banded karyotyping and metaphase FISH

A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46, XY, t(9; 22)(q34; q11.2)[12]/47, idem,+der(22)t(9; 22)[5]/46, XY[3]. Interphase FISH revealed nuc ish(ABL1, BCR) × 3(ABL1 con BCR × 2)[329/450]/(ABL1, BCR) × 4(ABL1 con BCR × 3)[5/450]/(AL1, BCR) × 3(ABL1 con BCR × 1)[44/450]. Metaphase FISH showed ish (9; 22)(ABL1+, BCR1+; BCR+, ABL+)[22]/der(22)(BCR+, ABL1+)[3]. The other case was that of a 31-yr-old male patient diagnosed with CML in the blastic phase. G-banded karyotyping of all 20 metaphase cells showed 47, XYYc, dup(1)(q21q32), del(7)(p11.2), t(9; 22)(q34; q11.2). Interphase FISH revealed nuc ish(ABL1, BCR) × 3(ABL1 con BCR × 2)[254/600]/(ABL1, BCR) × 3(ABL1 con BCR × 1)[191/600]. Metaphase FISH showed ish t(9; 22)(ABL1+, BCR+; BCR+, ABL1+)[16]. These results suggest that typical t(9; 22) and variant Ph may coexist in the same patient, and interphase FISH may facilitate the detection of the variant Ph that cannot be detected by G-banded karyotyping alone.