Spectral karyotyping and fluorescence in situ hybridization analyses identified a novel three-way translocation involving inversion 16 in therapy-related acute myeloid leukemia M4eo

We report a novel three-way translocation involving inversion 16 and chromosome 12 at bands 16p13, 16q22, and 12q24 in a patient with therapy-related acute myeloid leukemia (AML)-M4eo. Conventional G-banding of bone marrow cells at diagnosis was suggestive of inv(16)(p13q22) and a translocation of chromosomes 12 and 16. The presence of inv(16) was confirmed by reverse-transcription polymerase chain reaction (RT-PCR) analysis, which corresponded to the type A CBFB-MYH11 chimeric transcript. Spectral karyotyping (SKY) analysis clearly identified a reciprocal translocation between chromosomes 12 and 16. In addition, dual-color fluorescence in situ hybridization (FISH) analysis revealed a fusion signal for the CBFB and MYH11 probes and a signal for the MYH11 probe on the der(16) chromosome, as well as a signal for the CBFB probe on the der(12) chromosome. Thus, the karyotype was refined to 46,XX,der(12)t(12;16)(q24;q22),der(16)inv(16)(p13q22)t(12;16). Although we could not establish that this complex chromosomal aberration occurred either as a one-step, three-way event, or a sequential event with inv(16)(p13q22) followed by t(12;16)(q24;q22), SKY in combination with FISH and RT-PCR analyses successfully detected this complex chromosome abnormality in the patient.