RARBTranslocations in Acute Promyelocytic Leukemia without Raratranslocation

Introduction: Acute promyelocytic leukemia (APL) is defined by unique morphological features, typically abnormal promyelocytes containing azurophilic granules. Genomic basis of APL is characterized by the translocation t(15;17)(q22;q21), inducing fusions between promyelocytic leukemia (PML) and retinoic acid receptor-a (RARA). APL cells with PML-RARA respond to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), and recent clinical trials have achieved excellent outcome for typical APL with PML-RARA. Although a certain fraction of APL cases lacks PMR-RARA, most of them had translocation including RARAand other genes, namely, PLZF, NPM, and TBL1XR1. Eventually, all known APL-associated translocations involve RARA, accounting for 99% of APL. However, RARArearrangement is unable to be detected in the rest of APL cases, and molecular mechanisms underlying this small subset is still unclear. We here analyzed APL cases without RARAtranslocation, and identified a novel RARBfusion in the majority of patients with RARA-negative APL.