Coexistence of recurrent chromosomal abnormalities and the Philadelphia chromosome in acute and chronic myeloid leukemias: report of five cases and review of literature

Abstract

Progression of chronic myelogenous leukemia (CML) is frequently accompanied by cytogenetic evolution. Additional genetic abnormalities are seen in 10-20% of CML cases at the time of diagnosis, and in 60-80% of cases of advanced disease. Unbalanced chromosomal changes such as an extra copy of the Philadelphia chromosome (Ph), trisomy 8, and i(17)(q10) are common. Balanced chromosomal translocations, such as t(3;3), t(8;21), t(15;17), and inv(16) are typically found in acute myeloid leukemia, but rarely occur in CML. Translocations involving 11q23, t(8;21), and inv(16) are relatively common genetic abnormalities in acute leukemia, but are extremely rare in CML. In the literature to date, there are at least 76 Ph+ cases with t(3;21), 47 Ph+ cases with inv(16), 16 Ph+ cases with t(8;21), and 9 Ph+ cases with t(9;11). But most of what has been published is now over 30 years old, without the benefit of modern immunophenotyping to confirm diagnosis, and before the introduction of treatment regimes such as TKI. In this study, we explored the rare concomitant occurrence of coexistence current chromosomal translocation and t(9;22) in CML or acute myeloid leukemia (AML).

Keywords: Acute myeloid leukemia; Balanced chromosomal abnormalities; Chronic myelogenous leukemia; Clonal evolution; t(9;22).

Fig. 1

Bone marrow karyotype, metaphase-FISH, and fusion gene results of Case 1. a R-banded karyotype of case 1: 46,XY,der(9)t(9;22)(q34;q11.2)t(9;11)(p22;q23),der(11)t(9;11)(p22;q23),der(22)t(9;22)(q34;q11.2). Panels b-d represent FISH analyses of metaphase chromosomes corresponding to the karyotypes in panel a, b Metaphase FISH using dual color BCR-ABL1 fusion (ABL1: red; BCR: green). c Corresponding R-banded metaphase. d Sequential FISH using MLL-AF9 fusion (AF9: red; MLL: green) probe on the same metaphase cell, showing MLL-AF9 fusion. e BCR/ABL1 and MLL/AF9 results for patient 1. Red peak, BCR/ABL1; green peak, MLL/AF9 fusion gene transcripts; blue peak, internal reference gene ABL1

Fig. 2

Bone marrow karyotype, metaphase-FISH, and fusion gene results of Case 2. a R-banded karyotype of case 2: 47,XX,t(5;7)(q31;q21),der(9)t(9;22)(q34;q11.2)t(9;11)(p22;q23),der(11)t(9;11)(p22;q23),+21,der(22)t(9;22)(q34;q11.2). Panels b-d represent FISH analysis on metaphase cells corresponding to karyotypes in panels a and b Metaphase FISH using dual color BCR-ABL1 fusion (ABL1: red; BCR: green). c Corresponding R-banded metaphase. d Sequential FISH using MLL-AF9 fusion (AF9: red; MLL: green) probe on the same metaphase cell, showing its MLL-AF9 fusion. e Metaphase FISH using dual color break apart probe showing PDGFRB(5q32-q33) with PDGFRB fusion (fusion red/green signal). f Corresponding R-banded metaphase. g BCR/ABL1 and MLL/AF9 results for patient 2. Red peak, BCR/ABL1; green peak, MLL/AF9; blue peak, internal reference ABL1

Fig. 3

Bone marrow karyotype and metaphase-FISH results of Case 3. a R-banded karyotype of case 3: 47,XY,t(9;22)(q34;q11.2),inv(16)(p13;q22),+der(22)t(9;22)(q34;q11.2). Panels b-d represent FISH analysis on metaphase cells corresponding to the karyotypes in panel a, b Metaphase FISH using dual inv(16) with CBFB rearrangement (split red/green signal). c Corresponding R-banded metaphase. d FISH using BCR/ABL1 dual color fusion probe on a different metaphase cell, showing the BCR-ABL1 fusion(ABL1: red; BCR: green)

Fig. 4

Bone marrow karyotype and metaphase-FISH results of Case 4. a R-banded karyotype of case 4: 46,XY,t(3;21)(q26;q22),t(9;22)(q34;q11.2). Panels b-drepresent FISH analysis of metaphase cells corresponding to the karyotypes in panel a, b Metaphase FISH using dual color break apart probe EVI1 showing EVI1 rearrangement (split red/ green signal). c Corresponding R-banded metaphase. d Sequential FISH using BCR-ABL1 fusion (ABL1: red; BCR: green) probe on the same metaphase showing BCR-ABL1 fusion (ABL1: red; BCR: green)

Fig. 5

Bone marrow karyotype and interphase-FISH results of Case 5. a R-banded karyotype of case 5: 46,XY,t(9;22)(q34;q11.2),t(8;21)(q22;q22). Panels b-c represent FISH analysis on interphase cells corresponding to the karyotypes in panel a. b-c Interphase FISH using BCR/ABL1 (ABL1: red; BCR: green) dual color fusion probe, and RUNX1-RUNX1T1 (RUNX1: red; RUNX1T1: green) dual color fusion probe on different interphase cells showing a fused red-green (BCR‑ABL1) signal (yellow) and fused red-green (RUNX1-RUNX1T1) signal (yellow)