Abstract
The expression of p185(Bcr-Abl) in Ba/F3 cells inhibits the chemotactic response of these cells to SDF1alpha. A mutant p185(Bcr-Abl) with deletion of amino acids from 176 to 426 (p185(Delta176-426)) is deficient in suppressing SDF1alpha-stimulated chemotaxis. Comparison of the gene expression profiles among parental Ba/F3 cells and cells transformed by p185(Bcr-Abl) and p185(Delta176-426) reveals that class II phosphoinositide 3-kinase gamma (PI3KC2gamma) expression is markedly down-regulated by p185(Bcr-Abl) but not p185(Delta176-426). Furthermore, knockdown of PI3KC2gamma expression in p185(Delta176-426) cells is sufficient to suppress SDF1alpha-stimulated chemotaxis and to promote infiltration of these cells into the liver. Together, these studies suggest that inhibition of PI3KC2gamma expression may represent a mechanism by which Bcr-Abl suppresses SDF1alpha-induced chemotaxis and induces abnormal homing of leukemic cells.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cell Movement / drug effects
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Cell Transformation, Neoplastic / genetics
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Chemokine CXCL12 / pharmacology
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Chemotaxis / drug effects
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Chemotaxis / genetics
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Chemotaxis / physiology*
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Class Ib Phosphatidylinositol 3-Kinase
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Female
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism*
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Gene Expression Profiling
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Gene Expression Regulation, Leukemic
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Isoenzymes / genetics
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Isoenzymes / metabolism
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Leukemia, Experimental / genetics
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Leukemia, Experimental / metabolism
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Leukemia, Experimental / pathology
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
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Leukemic Infiltration
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Liver / metabolism
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Liver / pathology
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Mice
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Mice, Inbred BALB C
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Mutation
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Oligonucleotide Array Sequence Analysis
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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RNA Interference
Substances
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Chemokine CXCL12
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Isoenzymes
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Phosphatidylinositol 3-Kinases
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Class Ib Phosphatidylinositol 3-Kinase
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Pik3cg protein, mouse
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Fusion Proteins, bcr-abl