Requirement for cyclin D3 in lymphocyte development and T cell leukemias

Ewa Sicinska; Iannis Aifantis; Laurent Le Cam; Wojciech Swat; Christine Borowski; Qunyan Yu; Adolfo A. Ferrando; Steven D. Levin; Yan Geng; Harald Von Boehmer; Piotr Sicinski

doi:10.1016/S1535-6108(03)00301-5

Requirement for cyclin D3 in lymphocyte development and T cell leukemias

Ewa Sicinska, Iannis Aifantis, Laurent Le Cam, Wojciech Swat, Christine Borowski, Qunyan Yu, Adolfo A. Ferrando, Steven D. Levin, Yan Geng, Harald Von Boehmer, Piotr Sicinski

Division of Laboratory and Genomic Medicine

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

300 Scopus citations

Abstract

The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3 ^-/- animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.

Original language	English
Pages (from-to)	451-461
Number of pages	11
Journal	Cancer Cell
Volume	4
Issue number	6
DOIs	https://doi.org/10.1016/S1535-6108(03)00301-5
State	Published - Dec 2003

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@article{103c7ae8e405448f97c2affd72d77d84,

title = "Requirement for cyclin D3 in lymphocyte development and T cell leukemias",

abstract = "The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3 -/- animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.",

author = "Ewa Sicinska and Iannis Aifantis and {Le Cam}, Laurent and Wojciech Swat and Christine Borowski and Qunyan Yu and Ferrando, {Adolfo A.} and Levin, {Steven D.} and Yan Geng and {Von Boehmer}, Harald and Piotr Sicinski",

note = "Funding Information: We thank Dr. R.A. Weinberg, in whose laboratory this work was initiated, J. Liu-Donaher for blastocysts injections, T. Look, C. Lopez-Rodriguez, F. Gounari, A. Rao, N. Rao, H. Band, R.H. Medema, R. Bronson, E. Yu, W. Hahn, A. Hsieh, W. Sellers, and the members of the Sicinski laboratory for help and advice. This work was supported by an NIH R01 grant CA85296 (to P.S.). L.L.C. held Human Frontiers Science Postdoctoral Fellowship. A.A.F. was a fellow of the Leukemia Society. I.A. is supported by the Cancer Research Institute and the Leukemia Research Foundation.",

year = "2003",

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doi = "10.1016/S1535-6108(03)00301-5",

language = "English",

volume = "4",

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journal = "Cancer Cell",

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T1 - Requirement for cyclin D3 in lymphocyte development and T cell leukemias

AU - Sicinska, Ewa

AU - Aifantis, Iannis

AU - Le Cam, Laurent

AU - Swat, Wojciech

AU - Borowski, Christine

AU - Yu, Qunyan

AU - Ferrando, Adolfo A.

AU - Levin, Steven D.

AU - Geng, Yan

AU - Von Boehmer, Harald

AU - Sicinski, Piotr

N1 - Funding Information: We thank Dr. R.A. Weinberg, in whose laboratory this work was initiated, J. Liu-Donaher for blastocysts injections, T. Look, C. Lopez-Rodriguez, F. Gounari, A. Rao, N. Rao, H. Band, R.H. Medema, R. Bronson, E. Yu, W. Hahn, A. Hsieh, W. Sellers, and the members of the Sicinski laboratory for help and advice. This work was supported by an NIH R01 grant CA85296 (to P.S.). L.L.C. held Human Frontiers Science Postdoctoral Fellowship. A.A.F. was a fellow of the Leukemia Society. I.A. is supported by the Cancer Research Institute and the Leukemia Research Foundation.

PY - 2003/12

Y1 - 2003/12

N2 - The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3 -/- animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.

AB - The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3 -/- animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.

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U2 - 10.1016/S1535-6108(03)00301-5

DO - 10.1016/S1535-6108(03)00301-5

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SN - 1535-6108

VL - 4

SP - 451

EP - 461

JO - Cancer Cell

JF - Cancer Cell

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ER -

Requirement for cyclin D3 in lymphocyte development and T cell leukemias

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