Concomitant aberrant methylation of p15 and MGMT genes in acute myeloid leukemia: association with a particular immunophenotype of blast cells
| Autor: | Nada Suvajdžić, Nada Kraguljac Kurtovic, Koviljka Krtolica, Milena Krajnović, Jelica Jovanovic, Milica Colovic, Andrija Bogdanovic, Bogomir Dimitrijević |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Myeloid CD34 Kaplan-Meier Estimate Polymerase Chain Reaction 0302 clinical medicine Immunophenotyping Promoter Regions Genetic DNA Modification Methylases 0303 health sciences Methylation profile Hematology biology Myeloid leukemia General Medicine Methylation Middle Aged Flow Cytometry Prognosis 3. Good health Leukemia Myeloid Acute medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis DNA methylation Female MGMT Immunophenotype Adult medicine.medical_specialty Young Adult 03 medical and health sciences Internal medicine Biomarkers Tumor medicine Humans neoplasms Aged Cyclin-Dependent Kinase Inhibitor p15 030304 developmental biology Acute myeloid leukemia CD117 Tumor Suppressor Proteins DNA Methylation digestive system diseases DNA Repair Enzymes Immunology biology.protein Cancer research p15(INK4B) |
| Zdroj: | Medical Oncology |
| ISSN: | 1559-131X 1357-0560 |
| Popis: | In this study, methylation-specific polymerase chain reaction (MS-PCR) was used to define the methylation status of the target promoter sequences of p15 and MGMT genes in the group of 21 adult patients with acute myeloid leukemia (AML). The incidence of aberrant hypermethylation of p15 gene (71 %) was higher comparing to MGMT gene (33 %), whereas concomitant methylation of both genes had 24 % of the patients. Although the incidence of cytogenetic abnormalities between the groups with a different methylation status of p15 and/or MGMT genes was not significantly different, we observed general trend of clustering of abnormalities with adverse prognosis into groups with concomitant hypermethylation of both genes and only p15 gene. Also, we showed that AML patients with concomitant methylation of p15/MGMT genes had a higher proportion of leukemic blast cells characterized with specific expression of individual leukocyte surface antigens (CD117(+)/CD7(+)/CD34(+)/CD15(-)), indicating leukemic cells as early myeloid progenitors. Although we could not prove that hypermethylation of p15 and/or MGMT genes is predictive parameter for response to therapy and overall survival, we noticed that AML patients with comethylated p15/MGMT genes or methylated p15 gene exhibited a higher frequency of early death, lower frequency of complete remissions as well as a trend for shorter overall survival. Assessing of the methylation status of p15 and MGMT genes may allow stratification of patients with AML into distinct groups with potentially different prognosis. |
| Databáze: | OpenAIRE |
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