The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia

Acute promyelocytic leukaemia (APL) exhibits a characteristic t(15;17) tran slocation that fuses the promyelocytic leukaemia (PML) gene on 15q22 to the retinoic acid receptor alpha (RARA) gene on 17q12-q21.1. In a small subset of acute promyelocytic-like leukaemias (APL-L), RARA is fused to a differe nt partner: the promyelocytic leukaemia zinc finger (PLZF) gene on 11q23, t he nucleophosmin (NPM) gene on 5q35 or the nuclear mitotic apparatus (NuMA) gene on 11q13, We report on the molecular characterization of a RARA gene rearrangement in a patient with APL-L and demonstrate that the signal trans ducer and activator of transcription STAT5b gene is fused with RARA. STAT5b belongs to the janus kinase (JAK)-STAT signalling pathway. Remarkably, the STAT5b component of the chimeric protein is delocalized from the cytoplasm to the nucleus, where it displays a microspeckled pattern. Therefore, unus ual features of this APL-L might result from dysregulation of the JAK/STAT5 signal transducing pathways in the patient leukaemic cells. In this study, we identified STAT5b as a new gene fused to RARA in leukaemia; this is the first human tumour bearing a structurally abnormal STAT gene.