Acute promyelocytic leukemia and variant fusion proteins: PLZF-RARα fusion protein at a glance

Abstract

Classical acute promyelocytic leukemia (APL) cases are associated with the promyelocytic leukemia-retinoic acid receptor α (PML-RARα) chimeric fusion protein. Almost all the variant chimeric proteins share the same RARα component. Currently, more than 11 fusion partners of RARα have been identified, of which PML accounts for 95%, promyelocytic leukemia zinc finger (PLZF) take up2%, and the remaining are other variants. Although all-trans retinoic acid and arsenic trioxide have shown remarkable induction of molecular remission in classical APL, they have no appreciable effects on APL associated with other variant gene fusions (eg, PLZF-RARα and STAT5b-RARα). Here, we summarize all variant translocations, their key features, their leukemogenic potential as well as recent advances in studies of PLZF-RARα-associated APL. Basic pathogenic differences between classical APL and PLZF-RARα-associated APL are further discussed. We also highlight the critical leukemogenic events that are the backbone of these variant translocations so as to gain new insights into refractory APL.

Keywords: Acute promyelocytic leukemia; All-trans retinoic acid; Arsenic trioxide; Chimeric proteins; PLZF-RARα; Variant APL; ZBTB16-RARα.