AUTHOR=Merati Gabriele , Rossi Marianna , Gallì Anna , Roncoroni Elisa , Zibellini Silvia , Rizzo Ettore , Pietra Daniela , Picone Cristina , Rocca Barbara , Cabrera Claudia Patricia Tobar , Gelli Eleonora , Santacroce Eugenio , Arcaini Luca , Zappasodi Patrizia TITLE=Enrichment of Double RUNX1 Mutations in Acute Leukemias of Ambiguous Lineage JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.726637 DOI=10.3389/fonc.2021.726637 ISSN=2234-943X ABSTRACT=

Acute leukemia of ambiguous lineage (ALAL) is a rare type of leukemia and represents an unmet clinical need. In fact, due to heterogeneity, substantial rarity and absence of clinical trials, there are no therapeutic guidelines available. We investigated the genetic basis of 10 cases of ALAL diagnosed at our centre from 2008 and 2020, through a targeted myeloid and lymphoid sequencing approach. We show that this rare group of acute leukemias is enriched in myeloid-gene mutations. In particular we found that RUNX1 mutations, which have been found double mutated in 40% of patients and tend to involve both alleles, are associated with an undifferentiated phenotype and with lineage ambiguity. Furthermore, because this feature is typical of acute myeloid leukemia with minimal differentiation, we believe that our data strengthen the idea that acute leukemia with ambiguous lineage, especially those with an undifferentiated phenotype, might be genetically more closer to acute myeloid leukemia rather than acute lymphoblastic leukemia. These data enrich the knowledge on the genetic basis of ALAL and could have clinical implications as an acute myeloid leukemia (AML) – oriented chemotherapeutic approach might be more appropriate.