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PubMed · 40664914

RUNX1A isoform is overexpressed in acute myeloid leukemia and is associated with FLT3 internal tandem duplications.

Cosimo Cumbo·Francesco Tarantini·Elisa Parciante·Luisa Anelli·Antonella Zagaria·Giuseppina Biondi·Mariano Francesco Caratozzolo·Paola Orsini·Nicoletta Coccaro·Giuseppina Tota·Immacolata Redavid·Maria Rosa Conserva·Angela Minervini·Crescenzio Francesco Minervini·Vito Pier Gagliardi·Mario Delia·Flaviana Marzano·Claudia Telegrafo·Sharon Natasha Cox·Annalisa Natalicchio·Bachir Balech·Apollonia Tullo·Mattia Gentile·Francesco Giorgino·Giorgina Specchia·Pellegrino Musto·Francesco Albano
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Abstract

RUNX1A is the shortest and least expressed of the RUNX1 three main isoforms (A, B, C); despite this, the leukemogenic role of its overexpression has been clearly described. Several studies have shown RUNX1A involvement in different blood cancers and pilot observations in acute leukemia have been reported. In this context, we evaluated RUNX1 isoforms expression in a cohort of acute myeloid leukemia (AML) patients, finding overexpression of RUNX1A and RUNX1B, with higher median levels in thrombocytopenic cases. No difference was observed for RUNX1C. RUNX1A overexpression is higher in more immature AML phenotypes. According to the mutational profile, FLT3 internal tandem duplication (ITD) positive cases have the highest RUNX1A levels and the presence of FLT3-ITD was the only molecular variable able to influence RUNX1A expression. RUNX1A overexpression is disease-related, associated with a specific transcriptional profile, and reappears at relapse, with no clear kinetics except in FLT3-ITD cases. Overall, we demonstrate RUNX1A overexpression in AML and its association with the FLT3-ITD molecular subtype. Our data shed light on the dark side of RUNX1 deregulation, paving the way for further investigations.

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HumansLeukemia, Myeloid, AcuteCore Binding Factor Alpha 2 Subunitfms-Like Tyrosine Kinase 3MaleFemaleMiddle AgedProtein IsoformsAdultAgedTandem Repeat SequencesGene DuplicationYoung AdultAged, 80 and overGene Expression Regulation, LeukemicJournal Article

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Cosimo Cumbo, Francesco Tarantini, Elisa Parciante, Luisa Anelli, Antonella Zagaria, Giuseppina Biondi, Mariano Francesco Caratozzolo, Paola Orsini, Nicoletta Coccaro, Giuseppina Tota, Immacolata Redavid, Maria Rosa Conserva, Angela Minervini, Crescenzio Francesco Minervini, Vito Pier Gagliardi, Mario Delia, Flaviana Marzano, Claudia Telegrafo, Sharon Natasha Cox, Annalisa Natalicchio, Bachir Balech, Apollonia Tullo, Mattia Gentile, Francesco Giorgino, Giorgina Specchia, Pellegrino Musto, Francesco Albano. 2025-07-15. RUNX1A isoform is overexpressed in acute myeloid leukemia and is associated with FLT3 internal tandem duplications.. https://doi.org/10.1038/s41417-025-00939-z

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