Reduction of Prep1 Levels Affects Differentiation of Normal and Malignant B Cells and Accelerates Myc Driven Lymphomagenesis

Giorgio Iotti, Stefania Mejetta, Livia Modica, Dmitry Penkov, Maurilio Ponzoni, Francesco Blasi

Research output: Contribution to journalArticle

Abstract

The Prep1 homeodomain transcription factor has recently been recognized as a tumor suppressor. Among other features, haploinsufficiency of Prep1 is able to strongly accelerate the B-lymphomagenesis in EμMyc mice. Now we report that this occurs concomitantly with a change in the type of B-cell lymphomas generated by the Myc oncogene. Indeed, the tumors generated in the EμMyc-Prep1+/- mice are much more immature, being mostly made up of Pro-B or Pre-B cells, while those in the EμMyc-Prep1+/+ mice are more differentiated being invariably IgM+. Moreover, we show that Prep1 is in fact required for the differentiation of Pro-B and Pre-B cells into IgM+ lymphocytes and/or their proliferation, thus showing also how a normal function of Prep1 affects EμMyc lymphomagenesis. Finally, we show that the haploinsufficiency of Prep1 is accompanied with a major decrease of Myc-induced apoptosis and that the haploinsufficieny is sufficient for all these effects because the second allele of Prep1 is not lost even at late stages. Therefore, the tumor-suppressive activity of Prep1 is intertwined with both the interference with Myc-induced apoptosis as well as with natural developmental functions of the protein.

Original languageEnglish
Article numbere48353
JournalPLoS One
Volume7
Issue number10
DOIs
Publication statusPublished - Oct 25 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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