Molecular Characteristics and Clinical Significance of 12 Fusion Genes in Acute Promyelocytic Leukemia: A Systematic Review

Acute promyelocytic leukemia (APL) is characterized by the generation of the promyelocytic leukemia-retinoic acid (RA) receptor alpha (PML-RAR alpha) fusion gene. PML-RAR alpha is the central leukemia-initiating event in APL and is directly targeted by all-trans-RA (ATRA) as well as arsenic. In classic APL harboring PML-RAR alpha transcripts, more than 90% of patients can achieve complete remission when treated with ATRA combined with arsenic trioxide chemotherapy. In the last 20 years, more than 10 variant fusion genes have been found and identified in APL patients. These variant APL cases present different clinical phenotypes and treatment outcomes. All variant APL cases show a similar breakpoint within the RAR alpha gene, whereas its partner genes are variable. These fusion proteins have the ability to repress rather than activate retinoic targets. These chimeric proteins also possess different molecular characteristics, thereby resulting in variable sensitivities to ATRA and clinical outcomes. In this review, we comprehensively analyze various rearrangements in variant APL cases that have been reported in the literature as well as the molecular characteristics and functions of the fusion proteins derived from different RAR alpha partner genes and their clinical implications. (C) 2016 S. Karger AG, Basel