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• W4361824367 abstract "<div>Abstract<p>Translocations of retinoic acid receptor-α (<i>RARA</i>), typically <i>PML–RARA</i>, are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of <i>RARA</i>, we focused here on APL cases without <i>RARA</i> translocation to elucidate the molecular etiology of <i>RARA</i>-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without <i>RARA</i> translocations. Four of five <i>RARA</i>-negative APL cases had translocations involving retinoic acid receptor-β (<i>RARB</i>) translocations, and <i>TBL1XR1–RARB</i> was identified as an in-frame fusion in three cases; one case had an <i>RARB</i> rearrangement detected by FISH, although the partner gene could not be identified. When transduced in cell lines, <i>TBL1XR1–RARB</i> homodimerized and diminished transcriptional activity for the retinoic acid receptor pathway in a dominant-negative manner. <i>TBL1XR1–RARB</i> enhanced the replating capacity of mouse bone marrow cells and inhibited myeloid maturation of human cord blood cells as <i>PML–RARA</i> did. However, the response of APL with <i>RARB</i> translocation to retinoids was attenuated compared with that of <i>PML–RARA</i>, an observation in line with the clinical resistance of <i>RARB</i>-positive APL to ATRA. Our results demonstrate that the majority of <i>RARA</i>-negative APL have <i>RARB</i> translocations, thereby forming a novel, distinct subgroup of APL. <i>TBL1XR1–RARB</i> as an oncogenic protein exerts effects similar to those of <i>PML–RARA</i>, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL.</p><p><b>Significance:</b> These findings report a novel and distinct genetic subtype of acute promyelocytic leukemia (APL) by illustrating that the majority of APL without RARA translocations harbor RARB translocations. <i>Cancer Res; 78(16); 4452–8. ©2018 AACR</i>.</p></div>" @default.
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• W4361824367 date "2023-03-31" @default.
• W4361824367 modified "2023-10-16" @default.
• W4361824367 title "Data from Recurrent <i>RARB</i> Translocations in Acute Promyelocytic Leukemia Lacking <i>RARA</i> Translocation" @default.
• W4361824367 doi "https://doi.org/10.1158/0008-5472.c.6510653.v1" @default.
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