A small molecule Abl kinase inhibitor induces differentiation of Abelson virus-transformed pre-B cell lines

Nat Immunol. 2003 Jan;4(1):31-7. doi: 10.1038/ni870. Epub 2002 Dec 2.


Abelson murine leukemia virus-transformed cell lines have provided a critical model system for studying the regulation of B cell development. However, transformation by v-Abl blocks B cell development, resulting in the arrest of these transformants in an early pre-B cell-like state. We report here that treatment of Abelson virus-transformed pre-B cell lines with the small molecule Abl kinase inhibitor (STI571) results in their differentiation to a late pre-B cell-like state characterized by induction of immunoglobulin (Ig) light chain gene rearrangement. DNA microarray analyses enabled us to identify two genes inhibited by v-Abl that encode the Igk 3' enhancer-binding transcription factors Spi-B and IRF-4. We show that enforced expression of these two factors is sufficient to induce germline Igk transcription in Abelson-transformed pro-B cell lines. This suggests a key role for these factors, and perhaps for c-Abl itself, in the regulated activation of Ig light chain gene rearrangement.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abelson murine leukemia virus* / genetics
  • Abelson murine leukemia virus* / pathogenicity
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology*
  • Base Sequence
  • Benzamides
  • Cell Differentiation / drug effects
  • Cell Line, Transformed
  • DNA / genetics
  • DNA-Binding Proteins / genetics
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Profiling
  • Gene Rearrangement, B-Lymphocyte, Light Chain / drug effects
  • Imatinib Mesylate
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Oncogene Proteins v-abl / antagonists & inhibitors*
  • Piperazines
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Pyrimidines / pharmacology
  • Transcription Factors / genetics


  • Benzamides
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Oncogene Proteins v-abl
  • Piperazines
  • Pyrimidines
  • Transcription Factors
  • SPIB protein, human
  • Imatinib Mesylate
  • DNA
  • Protein-Tyrosine Kinases