Inhibition of class II phosphoinositide 3-kinase gamma expression by p185(Bcr-Abl) contributes to impaired chemotaxis and aberrant homing of leukemic cells

Leuk Lymphoma. 2010 Jun;51(6):1098-107. doi: 10.3109/10428191003754624.


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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Movement / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Chemokine CXCL12 / pharmacology
  • Chemotaxis / drug effects
  • Chemotaxis / genetics
  • Chemotaxis / physiology*
  • Class Ib Phosphatidylinositol 3-Kinase
  • Female
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation, Leukemic
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / metabolism
  • Leukemia, Experimental / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemic Infiltration
  • Liver / metabolism
  • Liver / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism*
  • RNA Interference


  • Chemokine CXCL12
  • Isoenzymes
  • Phosphatidylinositol 3-Kinases
  • Class Ib Phosphatidylinositol 3-Kinase
  • Pik3cg protein, mouse
  • Fusion Proteins, bcr-abl