RARbeta2 is a candidate tumor suppressor gene in myelofibrosis with myeloid metaplasia

Oncogene
Letetia C JonesH Phillip Koeffler

Abstract

Myelofibrosis with myeloid metaplasia (MMM) is a clonal stem-cell disorder that leads to ineffective hematopoiesis, bone marrow fibrosis, and extramedullary hematopoiesis. The molecular mechanisms underlying the development of this myeloproliferative syndrome are currently unknown. In order to identify tumor suppressor genes that may be involved in the disease process, we performed an analysis for loss of heterozygosity (LOH) in CD34+ cells from 29 patients with MMM. We observed a frequency of allelic loss on chromosomal arm 3p in 24% of cases. Detailed mapping of 3p revealed a distinct region of deletion at 3p24. Among the genes known to map within this region is the retinoic acid receptor-beta (RARbeta2) gene. To determine whether RARbeta2 gene activity is diminished in this disease, we analysed its expression in CD34+ cells from 17 patients with MMM using quantitative PCR. Our results indicate that expression of RARbeta2 is significantly decreased in 100% of patient samples compared to that in CD34+ cells from 10 normal individuals. Since allelic loss at 3p24 occurs in <25% of patients, we investigated the contribution of epigenetic modifications to RARbeta2 inactivity. Using methylation-specific PCR, we found hypermethylati...Continue Reading

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Citations

Feb 4, 2006·Current Opinion in Hematology·Ayalew Tefferi
May 27, 2009·Current Opinion in Hematology·Giovanni Barosi, Vittorio Rosti
Oct 5, 2013·Haematologica·John O MascarenhasRonald Hoffman
Sep 6, 2014·Best Practice & Research. Clinical Haematology·John Mascarenhas
Dec 5, 2008·Leukemia & Lymphoma·Ayalew Tefferi
Apr 5, 2011·Expert Opinion on Pharmacotherapy·Giovanni BarosiAlessandro M Vannucchi
May 2, 2012·Immunology Letters·Nicolas Serafin-HigueraPatricio Gariglio
May 20, 2011·Leukemia Research·Seisho TakeuchiH Phillip Koeffler
Jun 16, 2009·Journal of Cellular and Molecular Medicine·Alessandro M VannucchiTiziano Barbui
May 31, 2008·Stem Cells·Costanza BoganiUNKNOWN Myeloproliferative Disorders Research Consortium
Jan 13, 2009·British Journal of Haematology·Alexey V DanilovKenneth B Miller
Oct 8, 2005·Seminars in Hematology·Giovanni Barosi, Ronald Hoffman
Nov 19, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ayalew Tefferi
Nov 25, 2004·Hematology·Stephen O'BrienPeter Valent
Aug 2, 2006·Archives of Pathology & Laboratory Medicine·Arsalan Ahmed, Chung-Che Jeff Chang

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