Lopez, SophieVoisset, EdwigeTisserand, Julie CMosca, CyndiePrebet, ThomasSantamaria, DavidDubreuil, PatriceDe Sepulveda, Paulo2019-12-232019-12-232016-08-09Oncotarget. 2016;7 (32):51163-51173.1949-2553http://hdl.handle.net/20.500.12105/8876CDK4/CDK6 and RB proteins drive the progression through the G1 phase of the cell cycle. In acute myeloid leukemia (AML), the activity of the CDK/Cyclin D complex is increased. The mechanism involved is unknown, as are the respective roles played by CDK4 or CDK6 in this process. Here, we report that AML cells carrying FLT3-ITD mutations are dependent on CDK6 for cell proliferation while CDK4 is not essential. We showed that FLT3-ITD signaling is responsible for CDK6 overexpression, through a pathway involving the SRC-family kinase HCK. Accordingly, FLT3-ITD failed to transform primary hematopoietic progenitor cells from Cdk6-/- mice. Our results demonstrate that CDK6 is the primary target of CDK4/CDK6 inhibitors in FLT3-ITD positive AML. Furthermore, we delineate an essential protein kinase pathway -FLT3/HCK/CDK6- in the context of AML with FLT3-ITD mutations.engVoRhttp://creativecommons.org/licenses/by-nc-sa/4.0/AMLSRCOncogenePalbociclibProtein kinaseSignalingAnimalsCell Line, TumorCyclin-Dependent Kinase 6Gene Expression Regulation, LeukemicHumansLeukemia, Myeloid, AcuteMiceMice, Inbred C57BLMice, KnockoutMutationProto-Oncogene Proteins c-hckSignal TransductionTandem Repeat Sequencesfms-Like Tyrosine Kinase 3Atribución-NoComercial-CompartirIgual 4.0 Internacional2732339973251163-5117310.18632/oncotarget.99651949-2553Oncotargetopen access