A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis

Miaofen G. Hu, Amit Deshpande, Miriam Enos, Daqin Mao, Elisabeth A. Hinds, Guo Fu Hu, Rui Chang, Zhuyan Guo, Marei Dose, Changchuin Mao, Philip N. Tsichlis, Fotini Gounari, Philip W. Hinds

Research output: Contribution to journalArticlepeer-review


Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies.

Original languageEnglish (US)
Pages (from-to)810-818
Number of pages9
JournalCancer research
Issue number3
StatePublished - Feb 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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