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

doi:10.1158/0008-5472.CAN-08-2473

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

Immunology

Research output: Contribution to journal › Article › peer-review

Abstract

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 language	English (US)
Pages (from-to)	810-818
Number of pages	9
Journal	Cancer research
Volume	69
Issue number	3
DOIs	https://doi.org/10.1158/0008-5472.CAN-08-2473
State	Published - Feb 1 2009

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-08-2473

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title = "A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis",

abstract = "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.",

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

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doi = "10.1158/0008-5472.CAN-08-2473",

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T1 - A requirement for cyclin-dependent kinase 6 in thymocyte development and tumorigenesis

AU - Hu, Miaofen G.

AU - Deshpande, Amit

AU - Enos, Miriam

AU - Mao, Daqin

AU - Hinds, Elisabeth A.

AU - Hu, Guo Fu

AU - Chang, Rui

AU - Guo, Zhuyan

AU - Dose, Marei

AU - Mao, Changchuin

AU - Tsichlis, Philip N.

AU - Gounari, Fotini

AU - Hinds, Philip W.

PY - 2009/2/1

Y1 - 2009/2/1

N2 - 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.

AB - 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.

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SN - 0008-5472

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SP - 810

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JO - Cancer Research

JF - Cancer Research

IS - 3

ER -

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

Abstract

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