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

Cancer Gene Therapy volume 32, pages 963–972 (2025)Cite this article

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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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Fig. 1: RUNX1 isoforms molecular quantification in AML.
Fig. 2: Distribution of RUNX1A levels in AML.
Fig. 3: RUNX1A, kinetics and RNA-Seq data analysis.
Fig. 4

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Data availability

The data generated in this study are available upon request from the corresponding author.

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Acknowledgements

This work was supported by “Associazione Italiana contro le Leucemie (AIL)-BARI”.

Funding

This project received support from a grant awarded by Fondazione GIMEMA (Fondo per le Idee, 2021 edition).

Author information

Author notes

  1. These authors contributed equally: Cosimo Cumbo, Francesco Tarantini, Elisa Parciante.

Authors and Affiliations

  1. Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J) - Hematology and Stem Cell Transplantation Unit - University of Bari “Aldo Moro”, Bari, Italy

    Cosimo Cumbo, Francesco Tarantini, Elisa Parciante, Luisa Anelli, Antonella Zagaria, Nicoletta Coccaro, Giuseppina Tota, Immacolata Redavid, Maria Rosa Conserva, Angela Minervini, Crescenzio Francesco Minervini, Vito Pier Gagliardi, Mario Delia, Pellegrino Musto & Francesco Albano

  2. Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari “Aldo Moro”, Bari, Italy

    Giuseppina Biondi, Annalisa Natalicchio & Francesco Giorgino

  3. Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM) - National Research Council (CNR), Bari, Italy

    Mariano Francesco Caratozzolo, Flaviana Marzano, Claudia Telegrafo, Bachir Balech & Apollonia Tullo

  4. Department of Human Reproductive Medicine, Medical Genetics Unit, ASL Bari, Bari, Italy

    Paola Orsini & Mattia Gentile

  5. Department of Biosciences, Biotechnology and Environment, University of Bari “Aldo Moro”, Bari, Italy

    Sharon Natasha Cox

  6. School of Medicine, University of Bari “Aldo Moro”, Bari, Italy

    Giorgina Specchia

Authors
  1. Cosimo Cumbo
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  2. Francesco Tarantini
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Contributions

Conception and design of the study: CC and FA. Acquisition of data and/or analysis and interpretation of data: CC, FT, EP, LA, AZ, NC, GT, IR, MRC, AM, CFM, GS, PM, and FA. Clinical data acquisition: FT, VPG, and MD. Protein quantification: GB, AN, and FG. RNA-sequencing: MFC, FM, CT, SNC, BB and AT. Methylation analysis: PO and MG. Drafting of the manuscript: FA. All authors revised the manuscript for important intellectual content and approved the final version submitted for publication.

Corresponding author

Correspondence to Francesco Albano.

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The authors declare no competing interests.

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The local Ethics Committee of “Azienda Ospedaliero Universitaria Policlinico di Bari” approved the study. Informed consent was obtained from all patients before study inclusion, in accordance with the Declaration of Helsinki. Patients’ records/information were anonymized and de-identified before analysis.

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Cumbo, C., Tarantini, F., Parciante, E. et al. RUNX1A isoform is overexpressed in acute myeloid leukemia and is associated with FLT3 internal tandem duplications. Cancer Gene Ther 32, 963–972 (2025). https://doi.org/10.1038/s41417-025-00939-z

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