Article
SF3B1 mutations provide genetic vulnerability to copper ionophores in human acute myeloid leukemia.
Science advances - 22 Mar 2024
Moison Céline, Gracias Deanne, Schmitt Julie, Girard Simon, Spinella Jean-François, Fortier Simon, Boivin Isabel, Mendoza-Sanchez Rodrigo, Thavonekham Bounkham, MacRae Tara, Mayotte Nadine, Bonneil Eric, Wittman Mark, Carmichael James, Ruel Réjean, Thibault Pierre, Hébert Josée, Marinier Anne, Sauvageau Guy
Abstract excerpt
In a phenotypical screen of 56 acute myeloid leukemia (AML) patient samples and using a library of 10,000 compounds, we identified a hit with increased sensitivity toward SF3B1-mutated and adverse risk AMLs. Through structure-activity relationship studies, this hit was optimized into a potent, specific, and nongenotoxic molecule called UM4118. We demonstrated that UM4118 acts as a copper ionophore that initiates...
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