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

摘要

Classical acute promyelocytic leukemia (APL) cases are associated with the promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) chimeric fusion protein. Almost all the variant chimeric proteins share the same RAR alpha component. Currently, more than 11 fusion partners of RARa 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-RAR alpha and STAT5b-RAR alpha). Here, we summarize all variant translocations, their key features, their leukemogenic potential as well as recent advances in studies of PLZF-RAR alpha-associated APL. Basic pathogenic differences between classical APL and PLZF-RAR alpha-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. (C) 2019 Elsevier Inc. All rights reserved.