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The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus

Hugues de Thé 1 Christine Chomienne 2, 3 Michel Lanotte 4, 3 Laurent Degos 2, 3 Anne Dejean 1
1 Recombinaison et expression génétique
Institut Pasteur [Paris], INSERM - Institut National de la Santé et de la Recherche Médicale : U 163, CNRS - Centre National de la Recherche Scientifique : URA 271
Abstract : Retinoic acid is a vitamin A derivative with striking effects on development and cell differentiation. Several nuclear retinoic acid receptors (RARs), acting as ligand-inducible transcription factors, have been characterized and indirect evidence suggests that they have distinct roles. One of the most intriguing properties of retinoic acid is its ability to induce in vivo differentiation of acute promyelocytic leukaemia (APL) cells into mature granulocytes, leading to morphological complete remissions. Because the RAR alpha gene maps to chromosome 17q21 (ref. 14), close to the t(15;17) (q21-q11-22) translocation specifically associated with APL, we analysed RAR alpha gene structure and expression in APL cells. We report here that, in one APL-derived cell line, the RAR alpha gene has been translocated to a locus, myl, on chromosome 15, resulting in the synthesis of a myl/RAR alpha fusion messenger RNA. Using two probes located on either side of the cloned breakpoint, we have found genomic rearrangements of one or other locus in six patients out of eight, demonstrating that the RAR alpha and/or myl genes are frequently rearranged in APL and the breakpoints are clustered. These findings strongly implicate retinoic acid receptor alpha in leukaemogenesis.
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Hugues de Thé, Christine Chomienne, Michel Lanotte, Laurent Degos, Anne Dejean. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus. Nature, Nature Publishing Group, 1990, 347 (6293), pp.558-561. ⟨10.1038/347558a0⟩. ⟨pasteur-03238321⟩

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