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) translocation 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 different partner: the pro-myelocytic leukaemia zinc finger (PLZF) gene on 11q23, the nucleophosmin (NPM) gene on 5q35 or the nuclear mitotic apparatus (NuMA) gene on 11q13. We report on the molecular characterization of a RARA gene re-arrangement in a patient with APL-L and demonstrate that the signal transducer 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, unusual 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.
Arnould
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Laboratoire de Génétique, UPRES-INRA 952, CHRU, Rue du Morvan, 54511 Vandoeuvre les Nancy, France.
Philippe
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C
Bourdon
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V
Gr goire
M J
MJ
Berger
R
R
Jonveaux
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P
D000368:Aged; D001854:Bone Marrow Cells / Q000648:ultrastructure; D002886:Chromosomes, Human, Pair 17; D004268:DNA-Binding Proteins / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D008297:Male; D008894:Milk Proteins; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D008894:Milk Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D011993:Recombinant Fusion Proteins; D000072482:Retinoic Acid Receptor alpha; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases