Publication Date:
2012-11-16
Description:
Abstract 1395 Aberrant hypermethylation of tumor suppressor genes plays an important role in the development of acute myeloid leukemia (AML). In order to investigate the expression pattern of DNA methyltransferases (DNMTs) in AML patients, we established a tissue microarray (TMA) on bone marrow biopsies of 127 patients diagnosed with AML, who received intensive treatment in our department between 1999 and 2008 and with available bone marrow histology specimens. Immunohistochemistry was performed on this TMA with antibodies against DNMT1, DNMT3A, DNMT3B, methylated cytosine (mC) and hydroxymethylated cytosine (hmC). 127 patients having received intensive treatment in our department and with available clinical follow-up data were analyzed. Median follow-up after diagnosis was 56 (range 0–133) months. Median age at diagnosis of these patients cohort was 63 (range 21 – 85) years, 52 patients (41%) were female, 75(59%) were male. 88 patients (70%) had de novo AML, 38 (30%) had secondary AML (sAML) evolving from antecedent myelodysplastic syndrome or after previous cytotoxic treatment. For one patient the information was not available. Cytogenetic and molecular genetic risk assessment was performed according to the classification published by the European Leukemia Network (ELN). Of the 120 patients (95%) with available results, 20 patients (16.7%) were low risk, 49 (40.8%) intermediate-I, 20 (16.7%) intermediate-II and 31 (25.8%) high risk. Of 126 patients with evaluable DNMT1 expression, only 9 patients (7%) had detectable expression in ≥5% positive blasts. DNMT1 expression did not associate with any outcome parameter. DNMT3A expression analysis could not be established due to unspecific staining. By contrast, DNMT3B expression was positive (≥5%) in 80 of 116 evaluable patients (69%). Patients with absent or low (positivity in
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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