2024-03-19T10:49:08Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/88762022-11-07T13:32:37Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Lopez, Sophie
author
Voisset, Edwige
author
Tisserand, Julie C
author
Mosca, Cyndie
author
Prebet, Thomas
author
Santamaria, David
author
Dubreuil, Patrice
author
De Sepulveda, Paulo
author
2016-08-09
CDK4/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.
Oncotarget. 2016;7 (32):51163-51173.
1949-2553
http://hdl.handle.net/20.500.12105/8876
27323399
10.18632/oncotarget.9965
1949-2553
Oncotarget
AML
SRC
Oncogene
Palbociclib
Protein kinase
Signaling
An essential pathway links FLT3-ITD, HCK and CDK6 in acute myeloid leukemia