Combined Menin and XPO1 inhibition drive synergistic antileukemic activity in KMT2A r and NPM1 -m AML

bioRxiv (Cold Spring Harbor Laboratory) 2026 Preprint Open access

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Authors: Md. Hafiz Uddin, Sandhya Dhiman, Yufen Han, Amro Aboukameel, Vikram Dhillon, Jeff Justin Aguilar, Steven A. Buck, Abhinav Deol, Julie L. Boerner, Lisa Polin, Linda V. Kessler, Francis Burrows
+6 more Jay Yang, Asfar Sohail Azmi, Jaroslaw Pawel Maciejewski, Jevon A. Cutler, Yang Du, Suresh Kumar Balasubramanian
DOI: 10.64898/2026.03.10.710924
Cited by: 0
References: 41

Abstract

Abstract Menin scaffolds the oncogenic histone-lysine-N-methyltransferase (KMT2A)-fusion protein (FP) complex in KMT2A- r and wild-type KMT2A complex in NPM1 -m acute myeloid leukemia (AML). Menin inhibitors (MIs) are effective in KMT2A -r AML and NPM1 -m AML. However, not all patients respond to MIs as monotherapy. In this preclinical study, we demonstrate that the MI ziftomenib, in combination with the XPO1 inhibitor selinexor, synergistically inhibited the growth of multiple KMT2A- r and NPM1 -m AML cell lines (CI

Fields of Study & Subjects

Acute Myeloid Leukemia Research Retinoids in leukemia and cellular processes Chromatin Remodeling and Cancer

Publication details

Journal / source
bioRxiv (Cold Spring Harbor Laboratory)
Publication date
13 March 2026
Language
EN
Document type
Preprint