STUDY OF THE ROLE OF ABERRANT METHYLATION OF PROMOTER REGIONSOF SOX7, P15 INK4B AND PATHWAY ANTAGONIST GENES IN PATIENTS WITH MYELODYSPLASTIC SYNDROME
Epigenetic aberrations, includinghyper methylation of CpG islands in tumor-suppressor genes, are supposed to be a keymechanism of myelodysplastic syndrome (MDS)development. To find out the association between methylationstatus of SOX7, p15 INK4b, SFRP1, SFRP4 and SFRP5 genes and some hematological features and overallsurvival (OS), the data of 46 MDS patients withmedian age of 67.5 years were analyzed. MDSwas diagnosed according to WHO classification.Methylation-specific PCR was used to study themethylation status. Aberrant methylation of 1 and more genes wasfound in 43 patients (93.5%). The most frequentfindings were SOX7 (84.8%), SFRP1 (71.7 %) andp15 INK4b (54.3 %) genes methylation. Methylation of1, 2, 3, 4 and 5 genes simultaneously was detected in10.9 %, 28.3 %, 26.1 %, 19.6 % and 8.7 % ofpatients,respectively. There was no difference in the number of patientswith SFRP1, SFRP4, SOX7 and p15 nNK4b methylationin the groups with different bone marrow blastcounts. Methylation of SFRP5 gene was morefrequently seen in patients with refractory anemiawith excess of blasts (RAEB): 43.5% vs 13.0% inpatients without excess of blasts; OR = 5.1, 95 % CI:1.2-22.3, p = 0.047. The patients without excess ofblasts were characterized by methylation of 0-1genes: 26.1% vs 8.7% of RAEB patients, althoughthe difference was not significant. At the same time,there was the tendency to increased number of caseswith 3-5 methylated genes in patients with 10-19 % blasts compared to patients with 5-9 % blasts. In the whole MDS group, there was no correlation betweenthe number of methylated genes and patient’sage, number of bone marrow blasts or karyotype.Increased number of methylated genes did notinfluence the OS in the group of MDS patients. We conclude that MDS progression is associatedwith enhancement of epigenetic disturbances leadingto increase of the number of methylated genes, inparticular, SFRP5.