Abstract
Most childhood acute lymphoblastic leukemia (ALL) arises from early B-lineage cells,and response to steroid treatment is critical to successful ALL therapy. To investigate the effect of the pre-B cell receptor (pre-BCR) complex on the response of leukemic cells to steroids, cytoplasmic micro protein (cyto mu) was transfected into cyto mu-, steroid-resistant early B cell lines. The presence of cyto mu and the assembled pre-BCR complex conferred sensitivity to dexamethasone-induced apoptosis. Both intrinsic and extrinsic apoptosis pathways are involved in this cell death. However, if the transfected cyto micro protein is unable to assemble the pre-BCR complex, the cells remain resistant to dexamethasone. These findings suggest a role for the pre-BCR complex in the response of ALL cells to treatment and provide insight into the mechanism of steroid response in the treatment of pre-B ALL.
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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Apoptosis / drug effects
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Apoptosis / physiology
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B-Lymphocytes / pathology
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B-Lymphocytes / physiology
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Caspase 8
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Caspase 9
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Caspase Inhibitors
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Caspases / metabolism
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Dexamethasone / pharmacology*
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Down-Regulation
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Enzyme Activation
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Humans
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / physiology*
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Immunoglobulin mu-Chains / genetics
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Immunoglobulin mu-Chains / physiology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Pre-B Cell Receptors
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Receptors, Antigen, B-Cell
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Signal Transduction / physiology
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Transfection
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Tumor Cells, Cultured
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bcl-2-Associated X Protein
Substances
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Caspase Inhibitors
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Immunoglobulin Heavy Chains
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Immunoglobulin mu-Chains
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Membrane Glycoproteins
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Pre-B Cell Receptors
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Antigen, B-Cell
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bcl-2-Associated X Protein
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Dexamethasone
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CASP8 protein, human
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CASP9 protein, human
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases