Comprehensive Molecular and Functional Analysis of NUTM1-Rearranged Leukemia [cKitChIP-seq]

Mechanistically, BRD9-NUTM1 expression gives rise to distinctive open chromatin regions with global enhancement of H3K27Ac, particularly at loci associated with Myc, NF-κB, and posterior Hoxa genes. Notably, BRD9-NUTM1 leukemic cells responded robustly to cytarabine, in contrast to the relative resistance observed in KMT2A-r leukemias. Interestingly, our findings highlight a discrepancy observed in the clinical behavior of NUTM1-r leukemias, where the transformed cells display characteristics of stemness, yet tend to lose these properties under chemotherapy due to the dependence on active transcription.

Our findings delineate the unique molecular profile of NUTM1-r leukemias, suggesting opportunities for targeted therapies that exploit these specific vulnerabilities.