MLL rearrangement

The 3-year overall survival rates and event-free survival (EFS) rates were 80.7% and 69.4%, respectively. Multivariate Cox regression analysis revealed that gene MLL rearrangement (excluding MLL-AF9) (HR=3.071, 95%CI: 1.024-9.205) and positive molecular MRD after Induction Course Ⅱ therapy (HR=5.571, 95%CI: 1.244-24.957) were risk factors for EFS in pediatric AML patients.

We evaluate the latest data on various menin inhibitors-both as monotherapy and in combinations-emphasizing their efficacy and safety profiles. As new evidence continues to accumulate with recent drug approvals and ongoing randomized, phase 3 studies, menin inhibitors are rapidly becoming a component of the AML treatment paradigm for relapsed/refractory and likely newly diagnosed disease.

P2, N=31, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

Treatment with the dual EZH1/2 inhibitor UNC1999 and 5-azacytidine reactivated these PRC2 target genes, specifically in AML-HSPCs, toward normal gene expression patterns. These findings suggest that targeting Polycomb repression offers a promising epigenetic strategy for improving outcomes in KMT2A-rearranged AML.

P1/2, N=32, Active, not recruiting, Bambino Gesù Hospital and Research Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2025 --> Mar 2027

This uncovered consistent synergy between menin and lysine-specific demethylase 1 (LSD1) inhibition, including with the clinical agent iadademstat...In vivo, the combination produced potent antileukemic effects in both MOLM-13 and MLL-r patient-derived xenografts, markedly reducing leukemic burden and extending survival without overt toxicity. These findings identify LSD1 as a critical cofactor of the menin-MLL-LEDGF axis and establish concurrent menin and LSD1 inhibition as a mechanistically informed combinatorial therapeutic approach in MLL-r AML.

P2, N=22, Active, not recruiting, Masonic Cancer Center, University of Minnesota | Completed --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2026

P=N/A, N=200, Recruiting, Masonic Cancer Center, University of Minnesota | Trial completion date: Oct 2026 --> Feb 2027 | Trial primary completion date: Oct 2025 --> Feb 2026

Overall, we observed synergistic effects on differentiation induction and proliferation inhibition, both in vitro and in vivo. Together, our studies underscore the promise of this combination strategy as a novel therapeutic approach for improving treatment outcomes in patients with these specific genomic alterations.

P2, N=22, Completed, Masonic Cancer Center, University of Minnesota | Active, not recruiting --> Completed

P3, N=5949, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

The fetal barrier to transformation was enforced by the histone methyltransferase MLL3, and it could be overcome by cooperating mutations, such as NrasG12D. Heritable fetal protection against leukemic transformation may contribute to the low incidence of congenital and infant leukemias in humans.