title: Hypermethylation of the P15INK4b and P16INK4a in agnogenic myeloid metaplasia (AMM) and AMM in leukaemic transformation.
abstract: Hypermethylation of p15 and p16 genes was determined in 32 patients with agnogenic myeloid metaplasia(AMM), also known as idiopathic myelofibrosis (MF). These included 10 patients in leukaemic transformation phase. Using polymerase chain reaction-based methylation analysis assay methods, with substantiation using Southern blot analysis, the study showed no hypermethylation of p15 or p16 genes in the chronic phase of AMM, but p15 gene hypermethylation was found in four patients (40%) and p16 gene hypermethylation in two patients (20%) when they were in leukaemic transformation stage. Furthermore, two of the patients in leukaemic transformation were found to have both p15 and p16 gene hypermethylation, demonstrating possible multiple gene hypermethylation in the same patient. Thus, hypomethylation agents for treating patients with AMM in leukaemic transformation may be appropriate for future trials.
authors.affiliation: Division of Medical Oncology and Hematology, Brookdale University Hospital and Medical Center, Brooklyn, NY, USA. JCWANG5@aol.com
authors.forename: Jen C
authors.initials: JC
authors.lastname: Wang
authors.forename: Wilson
authors.initials: W
authors.lastname: Chen
authors.forename: Selvarany
authors.initials: S
authors.lastname: Nallusamy
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.forename: Allan D
authors.initials: AD
authors.lastname: Novetsky
mesh_terms: D015139:Blotting, Southern; D018797:Cell Cycle Proteins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D008745:Methylation; D016133:Polymerase Chain Reaction / Q000379:methods; D011230:Precancerous Conditions / Q000235:genetics; D055728:Primary Myelofibrosis / Q000235:genetics*; D025521:Tumor Suppressor Proteins
chemical_list: C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins