AUTHOR=Guarnera Luca , Ottone Tiziana , Fabiani Emiliano , Divona Mariadomenica , Savi Arianna , Travaglini Serena , Falconi Giulia , Panetta Paola , Rapanotti Maria Cristina , Voso Maria Teresa 

TITLE=Atypical Rearrangements in APL-Like Acute Myeloid Leukemias: Molecular Characterization and Prognosis

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.871590

DOI=10.3389/fonc.2022.871590

ISSN=2234-943X

ABSTRACT=<p>Acute promyelocytic leukemia (APL) accounts for 10–15% of newly diagnosed acute myeloid leukemias (AML) and is typically caused by the fusion of promyelocytic leukemia with retinoic acid receptor α (<italic>RARA</italic>) gene. The prognosis is excellent, thanks to the all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combination therapy. A small percentage of APLs (around 2%) is caused by atypical transcripts, most of which involve <italic>RARA</italic> or other members of retinoic acid receptors (<italic>RARB</italic> or <italic>RARG</italic>). The diagnosis of these forms is difficult, and clinical management is still a challenge for the physician due to variable response rates to ATRA and ATO. Herein we review variant APL cases reported in literature, including genetic landscape, incidence of coagulopathy and differentiation syndrome, frequent causes of morbidity and mortality in these patients, sensitivity to ATRA, ATO, and chemotherapy, and outcome. We also focus on non-RAR rearrangements, complex rearrangements (involving more than two chromosomes), and NPM1-mutated AML, an entity that can, in some cases, morphologically mimic APL.</p>