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ABERRANT METHYLATION OF PROMOTER REGIONS OF SOX7, P15INK4B AND WNT PATHWAY ANTAGONIST GENES IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES
Author(s): ,
Ivan Kostroma
Affiliations:
hematological clinic,Russian Institute of Hematology and Blood Transfusion,St.Petersburg,Russian Federation
,
Sergey Gritsaev
Affiliations:
hematological clinic,Russian Institute of Hematology and Blood Transfusion,St.Petersburg,Russian Federation
,
Zhanna Sidorova
Affiliations:
biochemical laboratory,Russian Institute of Hematology and Blood Transfusion,St.Petersburg,Russian Federation
,
Sergey Kapustin
Affiliations:
biochemical laboratory,Russian Institute of Hematology and Blood Transfusion,St.Petersburg,Russian Federation
Alexander Chechetkin
Affiliations:
hematological clinic,Russian Institute of Hematology and Blood Transfusion,St.Petersburg,Russian Federation
(Abstract release date: 05/19/16) EHA Library. Kostroma I. 06/09/16; 132750; E1201
Mr. Ivan Kostroma
Mr. Ivan Kostroma
Contributions
Abstract
Abstract: E1201

Type: Eposter Presentation

Background
Epigenetic aberrations, including hypermethylation of CpG islands in tumor-suppressor genes, are supposed to be a key mechanism of myelodysplastic syndrome (MDS) development.

Aims
To find out the association between methylation status of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes and some hematological features and overall survival (OS).

Methods
The data of 46 MDS patients with median age of 67.5 years were analyzed. MDS was diagnosed according to WHO classification. Methylation-specific PCR was used to study the methylation status.

Results
Aberrant methylation of ≥1 genes was found in 43 patients (93.5%). The most frequently findings were SOX7 (84.8%), SFRP1 (71.7%) and p15INK4b (54.3%) genes methylation. Methylation of 1, 2, 3, 4 and 5 genes simultaneously was detected in 10.9%, 28.3%, 26.1%, 19.6% and 8.7% of patients, respectively. There was no any difference in the number of patients with SFRP1, SFRP4, SOX7 and p15INK4b methylation in the groups with different bone marrow blasts counts. Methylation of SFRP5 gene was more frequently seen in patients with refractory anemia with excess of blasts (RAEB): 43.5% vs 13.0% in patients without excess of blasts; OR=5.1, 95%CI: 1.2-22.3, p=0.047. The patients without excess of blasts were characterized by methylation of 0-1 genes: 26.1% vs 8.7% of RAEB patients, although the difference was not significant. At the same time, there was the tendency to increase of the number of cases with 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 any correlation between the number of methylated genes and patient’s age, number of bone marrow blasts or karyotype. Increased number of methylated genes did not influence on the OS.

Conclusion
MDS progression is associated with enhancement of epigenetic disturbances leading to increase of the number of methylated genes, in particular, SFRP5

Session topic: E-poster
Abstract: E1201

Type: Eposter Presentation

Background
Epigenetic aberrations, including hypermethylation of CpG islands in tumor-suppressor genes, are supposed to be a key mechanism of myelodysplastic syndrome (MDS) development.

Aims
To find out the association between methylation status of SOX7, p15INK4b, SFRP1, SFRP4 and SFRP5 genes and some hematological features and overall survival (OS).

Methods
The data of 46 MDS patients with median age of 67.5 years were analyzed. MDS was diagnosed according to WHO classification. Methylation-specific PCR was used to study the methylation status.

Results
Aberrant methylation of ≥1 genes was found in 43 patients (93.5%). The most frequently findings were SOX7 (84.8%), SFRP1 (71.7%) and p15INK4b (54.3%) genes methylation. Methylation of 1, 2, 3, 4 and 5 genes simultaneously was detected in 10.9%, 28.3%, 26.1%, 19.6% and 8.7% of patients, respectively. There was no any difference in the number of patients with SFRP1, SFRP4, SOX7 and p15INK4b methylation in the groups with different bone marrow blasts counts. Methylation of SFRP5 gene was more frequently seen in patients with refractory anemia with excess of blasts (RAEB): 43.5% vs 13.0% in patients without excess of blasts; OR=5.1, 95%CI: 1.2-22.3, p=0.047. The patients without excess of blasts were characterized by methylation of 0-1 genes: 26.1% vs 8.7% of RAEB patients, although the difference was not significant. At the same time, there was the tendency to increase of the number of cases with 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 any correlation between the number of methylated genes and patient’s age, number of bone marrow blasts or karyotype. Increased number of methylated genes did not influence on the OS.

Conclusion
MDS progression is associated with enhancement of epigenetic disturbances leading to increase of the number of methylated genes, in particular, SFRP5

Session topic: E-poster

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