Faculty, Staff and Student Publications

Publication Date

10-1-2024

Journal

Leukemia

Abstract

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias.

Keywords

Humans, Proto-Oncogene Proteins, Child, Nucleophosmin, Adult, Leukemia, Leukemia, Myeloid, Acute, Leukaemia, Differentiation

DOI

10.1038/s41375-024-02368-7

PMID

39179671

PMCID

PMC11436367

PubMedCentral® Posted Date

8-23-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

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