Abstract
We studied the effects of Lyn ablation on the survival of drug-resistant chronic myelogenous leukemia (CML) blast crisis cells using siRNA. Lyn siRNA reduced Lyn protein in both normal hematopoietic cells and BCR-ABL1-expressing (BCR-ABL1(+)) blasts by 80-95%. Within 48 h, siRNA-treated BCR-ABL1(+) blasts underwent apoptosis, whereas normal cells remained viable. This increased dependence on Lyn signaling for BCR-ABL1(+) blast survival provides the basis for rational treatment of drug-resistant CML blast crisis, particularly when lymphoid in nature.
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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Apoptosis / physiology*
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Blast Crisis / metabolism*
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Blotting, Western
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Fusion Proteins, bcr-abl / metabolism*
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Humans
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In Situ Nick-End Labeling
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
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RNA Interference
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RNA, Small Interfering / metabolism*
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RNA, Small Interfering / physiology
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Signal Transduction / physiology
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Tetrazolium Salts
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Thiazoles
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Tumor Cells, Cultured
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src-Family Kinases / metabolism*
Substances
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RNA, Small Interfering
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Tetrazolium Salts
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Thiazoles
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Fusion Proteins, bcr-abl
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lyn protein-tyrosine kinase
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src-Family Kinases
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thiazolyl blue