Abstract
Chronic myeloid leukemia is caused by the tyrosine kinase oncoprotein BCR/ABL. Using oligonucleotide arrays to assay mRNAs at different phases of the cell cycle in BCR/ABL-transformed cells, we found that cyclin D2 mRNA was constitutively expressed at high levels throughout the cell cycle, a pattern confirmed by immunoblotting of protein lysates. Bone marrow cells from cyclin D2-deficient strains of mice failed to proliferate in response to infection with a retrovirus carrying BCR/ABL and failed to generate transformed lymphoid cell lines in vitro. These results establish that BCR/ABL promotes cell cycle progression by altering expression of cyclin D2 and that cyclin D2 induction plays a critical role in proliferation of hematopoietic cells by BCR/ABL.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bone Marrow Cells / cytology
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Cell Division / physiology
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Cell Line, Transformed
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Cell Transformation, Neoplastic / genetics*
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Cyclin D2
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Cyclins / biosynthesis
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Cyclins / genetics
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Cyclins / physiology*
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Fusion Proteins, bcr-abl / biosynthesis
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / physiology*
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Gene Expression Profiling
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology
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Genes, abl
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Hematopoietic Stem Cells / metabolism*
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Mice
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Oligonucleotide Array Sequence Analysis
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Signal Transduction
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Tetracycline / pharmacology
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Transcriptional Activation
Substances
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Ccnd2 protein, mouse
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Cyclin D2
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Cyclins
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RNA, Messenger
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Fusion Proteins, bcr-abl
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Tetracycline