A novel RARA–SNX15 fusion in PML–RARA-positive acute promyelocytic leukemia with t(11;17;15)(q13;q21.2;q24.1)

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Abstract
Acute promyelocytic leukemia (APL) is characterized by a series of retinoic acid receptor (RAR) fusion genes that lead to the dysregulation of RAR signaling and onset of APL. PML–RARA is the most common fusion generated from t(15;17)(q24;q21). In addition, the reciprocal fusion RARA–PML is present in over 80% of t(15;17) APL cases. The bcr3 types of RARA–PML and RARA–PLZF in particular are reciprocal fusions that contribute to leukemogenesis. Here, we report a variant APL case with t(11;17;15)(q13;q21.2;q24.1). Massive parallel sequencing of patient RNA detected the novel fusion transcripts RARA–SNX15 and SNX15–LINC02255 along with the bcr3 type of PML–RARA. Genetic analysis revealed that RARA–SNX15L is an in-frame fusion due to intron retention caused by RNA mis-splicing. RARA–SNX15L consisted mainly of SNX15 domains, including the Phox-homology domain, which has a critical role in protein–protein interactions among sorting nexins and with other partners. Co-immunoprecipitation analysis revealed that RARA–SNX15L is directly associated with SNX15 and with itself. Further studies are needed to evaluate the biological significance of RARA–SNX15L in APL. In conclusion, this is the first report of APL with a complex chromosomal rearrangement involving SNX15.

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