A new variant t(6;15;17)(q25;q22;q21) in acute promyelocytic leukemia: fluorescence in situ hybridization confirmation

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARα) at 17q21. The 2 chimeric genes PML/RARα and RARα/PML are thought to play a role in leukemogenesis. We report a case of APL in a patient carrying an apparently complex variant translocation identified as t(6;15;17) by R-banding and whole chromosome 15 and 17 painting. However, FISH analysis with a PML/RARα dual-color kit showed a more complex translocation, resulting presumably from a two-step rearrangement, with PML-RARα fusion gene located as expected on the der(15) but the residual 5'-RARα signal located on the der(6). The patient achieved complete remission with all-trans retinoic acid treatment associated with chemotherapy. This case illustrates the usefulness of combined cytogenetics, FISH, and molecular biology to evidence the PML/RARα fusion gene in complex cases.