Dataset Information

Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

ABSTRACT: D-type cyclins form complexes with cyclin-dependent kinases (CDK4/6) and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27(Kip1) and retinoblastoma tumor suppressor (Rb) is sufficient to rescue the development of Ccnd3(-/-) thymocytes. Furthermore, we show that a small molecule targeting the kinase function of cyclin D3:CDK4/6 inhibits both cell cycle entry in human T cell acute lymphoblastic leukemia (T-ALL) and disease progression in animal models of T-ALL. These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor.

SUBMITTER: Sawai CM

PROVIDER: S-EPMC3493168 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

Sawai Catherine M CM Freund Jacquelyn J Oh Philmo P Ndiaye-Lobry Delphine D Bretz Jamieson C JC Strikoudis Alexandros A Genesca Lali L Trimarchi Thomas T Kelliher Michelle A MA Clark Marcus M Soulier Jean J Chen-Kiang Selina S Aifantis Iannis I

Cancer cell 20121001 4

D-type cyclins form complexes with cyclin-dependent kinases (CDK4/6) and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27(Kip1) and retinoblastoma tumor suppressor (Rb) is sufficient to rescue the development of Ccnd3(-/-) thymocytes. Furthermore ...[more]

PMID: 23079656

Dataset Information

Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

Publications

Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

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