LAM-003, a new drug for treatment of tyrosine kinase inhibitor–resistant FLT3-ITD–positive AML
Beeharry N, Landrette S, Gayle S, Hernandez M, Grotzke JE, Young PR, Beckett P, Zhang X, Carter BZ, Andreeff M, Halene S, Xu T, Rothberg J, Lichenstein H. LAM-003, a new drug for treatment of tyrosine kinase inhibitor–resistant FLT3-ITD–positive AML. Blood Advances 2019, 3: 3661-3673. PMID: 31751472, PMCID: PMC6880894, DOI: 10.1182/bloodadvances.2019001068.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsCell Line, TumorDisease Models, AnimalDose-Response Relationship, DrugDrug Resistance, NeoplasmDrug SynergismEpigenesis, GeneticFms-Like Tyrosine Kinase 3Gene DuplicationGene Expression Regulation, LeukemicHumansLeukemia, Myeloid, AcuteMiceMutationProtein Kinase InhibitorsConceptsAcute myeloid leukemiaAML cell linesFLT3 inhibitorsFLT3-ITDSingle agentPositive acute myeloid leukemiaFLT3 inhibitor therapyStromal-conditioned mediumInitial clinical responseInternal tandem duplication mutationsFLT3-ITD patientsPoor patient prognosisXenograft mouse modelCell linesFLT3 kinase inhibitorsTandem duplication mutationsDiscovery of synergyWide CRISPR screenClinical responseTyrosine kinase receptorsInhibitor therapyPreclinical findingsBcl-2 inhibitorsMechanisms of resistancePatient prognosis