Methylation of the IL-12Rbeta2 gene as novel tumor escape mechanism for pediatric B-acute lymphoblastic leukemia cells

Cancer Research
Irma AiroldiVito Pistoia

Abstract

Previous studies have shown that the interleukin-12 receptor beta2 (IL-12Rbeta2) gene is expressed in normal naive, germinal center and memory B cells but not in their malignant counterparts. The aim of this study was to investigate (i) whether the IL-12Rbeta2 gene is silenced in B-cell acute lymphoblastic leukemia (B-ALL) cells, and (ii) what the functional implications of such silencing for tumor growth are. Here, we show that although mature B cells expressed both chains of the IL-12R, normal pro-B and pre-B cells failed to express the IL-12Rbeta2 chain. Similarly, primary tumor cells from pediatric pro-B, early pre-B, and pre-B ALL (30 cases) did not express the IL-12Rbeta2 chain. IL-12Rbeta2 gene silencing in B-ALL was found to depend on methylation of a CpG island in exon 1. Such methylation was not detected in normal early B cells that when differentiated into mature B cells expressed the IL-12Rbeta2 gene. Detection of IL-12Rbeta2 mRNA and protein in the tumorigenic 697 pre-B-ALL cell line allowed to perform functional experiments in severe combined immunodeficient/nonobese diabetic mice receiving 697 cells with or without human recombinant IL-12 (hrIL-12). hrIL-12 administration reduced tumor growth and metastasis throu...Continue Reading

References

Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·A S SternR Chizzonite
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·J G HermanS B Baylin
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·D H PreskyU Gubler
Oct 31, 1996·Annals of the New York Academy of Sciences·J MagramM K Gately
Dec 20, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·I AiroldiV Pistoia
Feb 4, 2003·Nature Reviews. Immunology·Giorgio Trinchieri

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Citations

Mar 18, 2015·Nature Reviews. Clinical Oncology·Kathryn G Roberts, Charles G Mullighan
Mar 31, 2015·Mediators of Inflammation·Rehana YasminNafees Ahmad
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Vito PistoiaIrma Airoldi
Jul 14, 2011·Journal of Leukocyte Biology·Irma Airoldi, Domenico Ribatti

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