Document Detail


Hypermethylation of GpG islands in the promoter region of p15(INK4b) in acute promyelocytic leukemia represses p15(INK4b) expression and correlates with poor prognosis.
MedLine Citation:
PMID:  12750706     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We evaluated the methylation status of p15 gene in a series of 65 patients with newly diagnosed acute promyelocytic leukemia (APL) receiving homogeneous treatment. Moreover, in 32 of them, the methylation status of p15 gene was correlated to the p15 m-RNA expression. In total, 31 patients had no p15 methylation (U group). An abnormal methylation pattern was found in 34 patients: in seven of these patients only methylated DNA was detected (M group), while in the remaining 27 patients (M/U group), both methylated and unmethylated DNA were amplified. Patients from M group showed a higher incidence of relapses and a lower disease-free survival (DSF) with respect to patients from U and M/U groups (29, 64 and 79% at 5 years for M, U/M and U patients, respectively, P=0.03), while p15 methylation had no impact on overall survival. The p15 expression was detectable in all patients with unmethylated DNA, in none of patients with fully methylated DNA and in 60% of patients with partially methylated DNA. The DFS estimate at 5 years for p15-negative patients was significantly lower than that of p15-positive patients (P=0.03). These data confirm that the presence of p15 methylation negatively influences the prognosis of APL, mainly when it represses the p15 gene transcription.
Authors:
L Teofili; M Martini; M Luongo; D Diverio; G Capelli; M Breccia; F Lo Coco; G Leone; L M Larocca
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Leukemia     Volume:  17     ISSN:  0887-6924     ISO Abbreviation:  Leukemia     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-16     Completed Date:  2003-06-04     Revised Date:  2013-03-04    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  919-24     Citation Subset:  IM    
Affiliation:
Department of Hematology, Catholic University Rome, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Bone Marrow / metabolism,  pathology
Cell Cycle Proteins / genetics*,  metabolism
Cyclin-Dependent Kinase Inhibitor p15
Cyclin-Dependent Kinase Inhibitor p16 / genetics*,  metabolism
DNA Methylation*
DNA Primers / chemistry
DNA, Neoplasm / genetics
Dinucleoside Phosphates / genetics*
Enzyme Inhibitors / metabolism
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Gene Silencing*
Genes, Tumor Suppressor
Humans
Immunoenzyme Techniques
Leukemia, Promyelocytic, Acute / genetics*,  pathology,  therapy
Male
Neoplasm Recurrence, Local / genetics
Polymerase Chain Reaction
Prognosis
Promoter Regions, Genetic / genetics*
RNA, Messenger / genetics,  metabolism
RNA, Neoplasm / genetics
Sulfites / metabolism
Survival Rate
Syndrome
Treatment Outcome
Tumor Suppressor Proteins*
Chemical
Reg. No./Substance:
0/CDKN2B protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/DNA Primers; 0/DNA, Neoplasm; 0/Dinucleoside Phosphates; 0/Enzyme Inhibitors; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Sulfites; 0/Tumor Suppressor Proteins; 3353-33-1/guanylyl-(3'-5')-guanosine
Comments/Corrections
Comment In:
Leukemia. 2003 May;17(5):839-40   [PMID:  12750694 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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