biostudies-literatureFischer KCWorldwide Cancer Research100149https://www.ebi.ac.uk/biostudies/studies/S-EPMC12549552biostudies-literatureUnknown2(4)Deregulated expression of the transcription factor c-MYC is well established as a primary driver of diverse tumor types. In this study, for the first time to our knowledge, we show that mouse and human myeloid leukemias provoked by oncogenic mixed lineage leukemia (MLL) fusion proteins are dependent on the MYC family member MNT (MAX network transcriptional repressor), which is highly expressed in these AMLs. To investigate the role of MNT, we generated <i>Mnt-</i>deletable murine <i>MLL::AF9</i> acute myeloid leukemias (AMLs), using the well-studied hemopoietic reconstitution model. <i>Mnt</i> deletion provoked the apoptosis of <i>MLL::AF9</i> AML cells in vitro and increased apoptosis elicited by the BH3 (BCL-2 homology region 3) mimetic drugs S63845 (MCL-1 (Myeloid cell leukemia-1) speciBlood neoplasiaMNT: a new target for AML.PMC1254955219-0232Litalien VCory SFischer KCKelly GLDiepstraten STWei AHBrown FCJahja MfalseMNT: a new target for AML.Deregulated expression of the transcription factor c-MYC is well established as a primary driver of diverse tumor types. In this study, for the first time to our knowledge, we show that mouse and human myeloid leukemias provoked by oncogenic mixed lineage leukemia (MLL) fusion proteins are dependent on the MYC family member MNT (MAX network transcriptional repressor), which is highly expressed in these AMLs. To investigate the role of MNT, we generated <i>Mnt-</i>deletable murine <i>MLL::AF9</i> acute myeloid leukemias (AMLs), using the well-studied hemopoietic reconstitution model. <i>Mnt</i> deletion provoked the apoptosis of <i>MLL::AF9</i> AML cells in vitro and increased apoptosis elicited by the BH3 (BCL-2 homology region 3) mimetic drugs S63845 (MCL-1 (Myeloid cell leukemia-1) speci2025-01-01T00:00:00Z2025 Nov2026-06-05T05:41:50.563Z2026-06-03T03:08:08.346ZS-EPMC125495524114044310.1016/j.bneo.2025.100149