Fig. 2: KMT2A rearrangement leads to leukemogenesis. | Leukemia

Fig. 2: KMT2A rearrangement leads to leukemogenesis.

From: Menin inhibitors in pediatric acute leukemia: a comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community

Fig. 2

A Interaction among KMT2A (MLL1), menin, and LEDGF. Menin binding sites are preserved during KMT2A rearrangement. B Cell differentiation and the gradual decrease of the HOX program. C The MLL1 fusion protein (MLL1-FP) leads to the overexpression of HOX cluster genes and MEIS1, contributing to the uncontrolled proliferation of undifferentiated precursor cells. D Novel synthesized menin inhibitors disrupt the menin-KMT2A interaction, effectively preventing the binding of MLL1-FP to promoter sites. This disruption halts the aberrant expression of HOX genes and MEIS1, resulting in the release of the differentiation block. Menin inhibitors disrupt NUP98 fusion occupancy at chromatin sites and disrupt MLL-NPM1 activity. This induces differentiation and reverses leukemogenesis by downregulating MEIS1 expression.

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