Acute promyelocytic leukemia with a STAT5b-RARα fusion transcript defined by array-CGH, FISH, and RT-PCR.

Acute promyelocytic leukemia (APL) is characterized by the generation of the PML-RARα fusion transcript as a result of a reciprocal chromosomal rearrangement, t(15;17)(q22;q12), with breakpoints within the PML gene and the RARα gene. In a small proportion of APL cases, RARα is fused with a number of alternative partner genes. The signal transducer and activator of transcription 5 beta (STAT5b) is one of the variant partners. Here, we describe one rare case with all-trans retinoic acid (ATRA) -unresponsive APL characterized by the STAT5b-RARα fusion transcript. Morphology and immunophenotypic analyses indicated the typical features of APL; however, cytogenetic analysis exhibited a normal karyotype, and importantly, results of interphase fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that PML-RARα expression was negative. FISH analysis with the RARα dual-color break-apart rearrangement probe indicated a submicroscopic deletion of the 3' end of one RARA gene. Indeed, the STAT5b-RARα fusion transcript was found in this case by array-based comparative genomic hybridization and nested RT-PCR. To the best of our knowledge, we report here only the sixth APL patient in the world with the STAT5b-RARα fusion transcript. Additional clinical studies concerning the prognosis, response to therapy, and pathogenesis of APL patients with STAT5b-RARα fusion are necessary.