Synergistic Activity of Combined FLT3-ITD and MDM2 Inhibition with Quizartinib and Milademetan in FLT3-ITD Mutant/TP53 Wild-type Acute Myeloid Leukemias
Zhang W, Li L, Muftuoglu M, Basyal M, Togashi N, Iwanaga K, Tanzawa F, Numata M, Bixby D, Erba H, Podoltsev N, Schiller G, Kumar P, Lesegretain A, Isoyama T, Seki T, Daver N, Andreeff M. Synergistic Activity of Combined FLT3-ITD and MDM2 Inhibition with Quizartinib and Milademetan in FLT3-ITD Mutant/TP53 Wild-type Acute Myeloid Leukemias. Clinical Cancer Research 2025, 31: 3033-3047. PMID: 40327322, PMCID: PMC12260509, DOI: 10.1158/1078-0432.ccr-24-2764.Peer-Reviewed Original ResearchAcute myeloid leukemiaMurine double minute 2Patient-derived xenograftsPatient-derived xenograft modelsFLT3-ITDMyeloid leukemiaMDM2 inhibitionCell linesInhibition of FLT3-ITDFLT3-mutant acute myeloid leukemiaDose-escalation clinical trialDevelopment of resistant diseaseFLT3 internal tandem duplicationOverexpression of murine double minute 2FLT3-ITD acute myeloid leukaemiaFMS-like tyrosine kinase 3Phase 1 clinical trialIncomplete hematologic recoveryRelapsed/refractory AML patientsTP53 wild typeReduced tumor burdenPreliminary clinical dataAcute myeloid leukemia cell linesMutations of FMS-like tyrosine kinase 3Expression of prosurvival
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