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Article
Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia
Blood
  • Kristen M. Sokalski, Schulich School of Medicine & Dentistry
  • Stephen K.H. Li, Schulich School of Medicine & Dentistry
  • Ian Welch, Western University
  • Heather Anne T. Cadieux-Pitre, Western University
  • Marek R. Gruca, Schulich School of Medicine & Dentistry
  • Rodney P. DeKoter, Schulich School of Medicine & Dentistry
Document Type
Article
Publication Date
9-8-2011
URL with Digital Object Identifier
10.1182/blood-2011-02-335539
Abstract

The E26 transformation-specific (Ets) transcription factor PU.1 is required to generate lymphoid progenitor cells from hematopoietic stem cells, but it is not required to generate B cells from committed B-cell lineage progenitors.We hypothesized that PU.1 function in B-cell differentiation is complemented by the related Ets transcription factor Spi-B. To test this hypothesis, mice were generated lacking both PU.1 and Spi-B in the B-cell lineage. Unlike mice lacking PU.1 or Spi-B, mice deficient in both PU.1 and Spi-B in the B-cell lineage had reduced frequencies of B cells as well as impaired B-cell differentiation. Strikingly, all PU.1 and Spi-B-deficient mice developed pre-B cell acute lymphoblastic leukemia before 30 weeks of age. Pre-B cells accumulated in the thymus resulting in massive thymic enlargement and dyspnea. These findings demonstrate that PU.1 and Spi-B are essential transcriptional regulators of B-cell differentiation as well as novel tumor suppressors in the B-cell lineage. © 2011 by The American Society of Hematology.

Citation Information
Kristen M. Sokalski, Stephen K.H. Li, Ian Welch, Heather Anne T. Cadieux-Pitre, et al.. "Deletion of genes encoding PU.1 and Spi-B in B cells impairs differentiation and induces pre-B cell acute lymphoblastic leukemia" Blood Vol. 118 Iss. 10 (2011) p. 2801 - 2808
Available at: http://works.bepress.com/rodney-dekoter/13/