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Abstract
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.
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Fig. 1.
Mechanism of detection of classical and variant Philadelphia chromosome (Ph) and signal patterns of FISH using dual color dual fusion probe. (A) Classical translocation showing G1R1F2. (B) One-step mechanism of variant Ph, showing G2R2F1. Three breaks and reciprocal rejoinings occur at the same time on chromosome 9, 22, and partner chromosome. (C) Two-step mechanism of variant Ph, showing G1R1F2. The standard t(9;22) is formed, and then, the segment of der(9) exchanges material with the variable partner chromosome. Modified from figure in reference [1].
Abbreviations: V, variable partner chromosome; G, green signal; R, red signal; F, fusion signal.
Fig. 2.
Cytogenetic findings of Case 1. (A) G-banded karyogram showing 47,XY,t(9;22)(q34;q11.2),+der(22)t(9;22). (B) Interphase FISH signal pattern showed G2R2F1 (left), suggesting one-step mechanism of variant Ph and G1R1F2 (right), indicating typical t(9;22). (C) Metaphase FISH showed G1R1F3 (left). Each fusion signal resides on the der(22)t(9;22),+der(22)t(9;22), and der(9)t(9;22). G1R1F2 (right) indicate typical t(9;22).
Abbreviations: G, green signal; R, red signal; F, fusion signal.
Fig. 3.
Cytogenetic findings of Case 2. (A) G-banded karyogram showing 47,XYYc,dup(1)(q21q32),del(7)(p11.2),t(9;22)(q34;q11.2). (B) Interphase FISH signal pattern of G2R2F1 (left), suggesting one-step mechanism of variant translocation and G1R1F2 (right), indicating typical t(9;22).
Table 1.
Follow-up data of karyotyping and FISH in case 1
Table 2.
Follow-up data of karyotyping and FISH in case 2
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