2026-08-29T22:06:56Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/88762024-11-30T01:12:33Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Ligue Nationale Contre le Cancer (Francia)
funder
Fondation ARC pour la recherche sur le cancer
2019-12-23T14:10:46Z
2019-12-23T14:10:46Z
2016-08-09
Oncotarget. 2016;7 (32):51163-51173.
10.18632/oncotarget.9965
1949-2553
1949-2553
Oncotarget
27323399
http://hdl.handle.net/20.500.12105/8876
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.
eng
AML
SRC
Oncogene
Palbociclib
Protein kinase
Signaling
An essential pathway links FLT3-ITD, HCK and CDK6 in acute myeloid leukemia
journal article
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AnEssentialPathwayLinksFLT3-ITD_2016.pdf
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AnEssentialPathwayLinks FLT3-ITD_supl.pdf
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AnEssentialPathwayLinksFLT3-ITD_2016+_table.docx
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