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

Overview

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.

publication date

  • October 16, 2012

Research

keywords

  • Cyclin D3
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Identity

PubMed Central ID

  • PMC3493168

Scopus Document Identifier

  • 84867602759

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2012.09.016

PubMed ID

  • 23079656

Additional Document Info

volume

  • 22

issue

  • 4