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

Cancer cell | 2012

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.

Pubmed ID: 23079656 RIS Download

Research resources used in this publication

None found

Antibodies used in this publication

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087
  • Agency: NCI NIH HHS, United States
    Id: R01CA133379
  • Agency: NCI NIH HHS, United States
    Id: R01 CA149655
  • Agency: NCI NIH HHS, United States
    Id: R01 CA105129
  • Agency: NIGMS NIH HHS, United States
    Id: R01GM088847
  • Agency: NCI NIH HHS, United States
    Id: R21 CA141399
  • Agency: NCI NIH HHS, United States
    Id: R01CA149655
  • Agency: NCI NIH HHS, United States
    Id: R01CA105129
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM088847
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016087-30
  • Agency: NCI NIH HHS, United States
    Id: 5 P30CA16087-31
  • Agency: NCI NIH HHS, United States
    Id: R01 CA133379
  • Agency: NCI NIH HHS, United States
    Id: R01 CA096899
  • Agency: NCI NIH HHS, United States
    Id: 5P30CA16087-31
  • Agency: NCI NIH HHS, United States
    Id: R21CA141399

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