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Hematology - Immunology - Oncology

Reduction of Prep1 Levels Affects Differentiation of Normal and Malignant B Cells and Accelerates Myc Driven Lymphomagenesis
Published: Thursday, October 25, 2012
Author: Giorgio Iotti et al.

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

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.