title: Prognostic impact of p15 gene aberrations in acute leukemia.
abstract: The p15 gene (also known as CDKN2B, INK4B, p15INK4B), located in band 9p21, encodes a protein that induces a G1-phase cell cycle arrest through inhibition of CDK4/6 (cyclin-dependent kinase 4/6). It also plays an important role in the regulation of cellular commitment of hematopoietic progenitor cells and myeloid cell differentiation. p15 can be silenced by several mechanisms, including deletion and hypermethylation of its promoter. Homozygous p15 deletion is rare in acute myeloblastic leukemia (AML) and myelodysplastic syndromes (MDS) but frequent in acute lymphoblastic leukemia (ALL). On the contrary, methylation of the p15 promoter is identified in some 50% of the patients with AML and MDS, but is less frequent in ALL. The analysis of the 28 studies available in the literature revealed conflicting results (unfavorable, favorable or no impact) that can be due, at least in part, to methodological and/or biological pitfalls. Among those, are the heterogeneity of the methylation patterns of the p15 gene and the lack of a comprehensive analysis including transcriptional and translational inactivation that have major impact on its expression. Therefore, detection of the p15 mRNA expression (quantitative or not) may represent a more appropriate method to determine the prognostic impact of the p15 gene.
authors.affiliation: a Laboratoire d'Histologie, Embryologie et Cytogénétique, Faculté de Médecine et des Sciences de la Santé , Université de Brest , Brest , France.|b Institut National de la Santé et de la Recherche Médicale (INSERM) , Brest , France.|c Service de Cytogénétique et Biologie de la Reproduction , Hôpital Morvan , CHRU Brest , Brest , France.
authors.forename: Marc
authors.initials: M
authors.lastname: De Braekeleer
authors.affiliation: a Laboratoire d'Histologie, Embryologie et Cytogénétique, Faculté de Médecine et des Sciences de la Santé , Université de Brest , Brest , France.|b Institut National de la Santé et de la Recherche Médicale (INSERM) , Brest , France.|c Service de Cytogénétique et Biologie de la Reproduction , Hôpital Morvan , CHRU Brest , Brest , France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Douet-Guilbert
authors.affiliation: d Haematological Cancer Genetics , Wellcome Trust Sanger Institute , Cambridge , UK.
authors.forename: Etienne
authors.initials: E
authors.lastname: De Braekeleer
mesh_terms: D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005787:Gene Frequency; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D058990:Molecular Targeted Therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000401:mortality*; D011379:Prognosis
chemical_list: D050762:Cyclin-Dependent Kinase Inhibitor p15
keywords: CDKN2B; INK4B; acute leukemia; myelodysplastic syndromes; p15; prognosis