ABERRANT METHYLATION OF PROMOTER REGIONS OF SOX7, P15INK4B AND WNT PATHWAY ANTAGONIST GENES IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Kostroma I. 06/09/16; 134550; PB1650
Mr. Ivan Kostroma
Contributions
Contributions
Abstract
Abstract: PB1650
Type: Publication Only
Background
Aberrant methylation of CpG islands of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and be associated with the natural history of the disease.
Aims
To reveal the features of aberrant methylation of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes in AML patients.
Methods
The data of 57 AML patients with median age of 51.0 years were analyzed. Next AML variants were diagnosed: 2 patients with M0, 7 M1, 23 M2, 4 M4, 8 M5, 3 M6 and 10 with myelodysplasia. Cytogenetic data were available in 56 patients. Normal karyotype was identified in 31 (54.4%) patients. Other 25 patients had different chromosomal aberrations including complex karyotype in 8 patients. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes.
Results
The frequency of aberrant methylation was next: SFRP1 68.4%, p15INK4b 63.2%, SOX7 47.4%, SFRP4 42.1%, SFRP5 35.1%. Absence of aberrant methylation was found in 5 (8.8%) patients. The most frequent finding was methylation of 2 and 3 genes simultaneously: 29.8% and 21.1% accordingly. Half of the patients with aberrant methylation status of all 5 studied genes had AML with dysplasia. The most part of patients with complex karyotype (62.5%) had aberrant methylation of 3-5 genes. The difference in the number of patients with complex or normal karyotype who had aberrant methylation of all 5 studied genes was significant: 50.0% vs 9.7% OR=9.3 95% CI 1.5-58.0; p=0.022. The patients with normal karyotype and without FLT3 and NPM1 mutations were separated according to the number of genes with aberrant methylation: 0-2 vs 3-5. There was no significant difference in overall and relapse free survival between these groups.
Conclusion
Aberrant methylation of SOX7, p15INK4b and Wnt pathway antagonist genes is recurrent biologic phenomenon in AML patients. More often this finding occurs in AML patients with myelodysplasia and complex karyotype.
Session topic: E-poster
Type: Publication Only
Background
Aberrant methylation of CpG islands of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and be associated with the natural history of the disease.
Aims
To reveal the features of aberrant methylation of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes in AML patients.
Methods
The data of 57 AML patients with median age of 51.0 years were analyzed. Next AML variants were diagnosed: 2 patients with M0, 7 M1, 23 M2, 4 M4, 8 M5, 3 M6 and 10 with myelodysplasia. Cytogenetic data were available in 56 patients. Normal karyotype was identified in 31 (54.4%) patients. Other 25 patients had different chromosomal aberrations including complex karyotype in 8 patients. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes.
Results
The frequency of aberrant methylation was next: SFRP1 68.4%, p15INK4b 63.2%, SOX7 47.4%, SFRP4 42.1%, SFRP5 35.1%. Absence of aberrant methylation was found in 5 (8.8%) patients. The most frequent finding was methylation of 2 and 3 genes simultaneously: 29.8% and 21.1% accordingly. Half of the patients with aberrant methylation status of all 5 studied genes had AML with dysplasia. The most part of patients with complex karyotype (62.5%) had aberrant methylation of 3-5 genes. The difference in the number of patients with complex or normal karyotype who had aberrant methylation of all 5 studied genes was significant: 50.0% vs 9.7% OR=9.3 95% CI 1.5-58.0; p=0.022. The patients with normal karyotype and without FLT3 and NPM1 mutations were separated according to the number of genes with aberrant methylation: 0-2 vs 3-5. There was no significant difference in overall and relapse free survival between these groups.
Conclusion
Aberrant methylation of SOX7, p15INK4b and Wnt pathway antagonist genes is recurrent biologic phenomenon in AML patients. More often this finding occurs in AML patients with myelodysplasia and complex karyotype.
Session topic: E-poster
Abstract: PB1650
Type: Publication Only
Background
Aberrant methylation of CpG islands of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and be associated with the natural history of the disease.
Aims
To reveal the features of aberrant methylation of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes in AML patients.
Methods
The data of 57 AML patients with median age of 51.0 years were analyzed. Next AML variants were diagnosed: 2 patients with M0, 7 M1, 23 M2, 4 M4, 8 M5, 3 M6 and 10 with myelodysplasia. Cytogenetic data were available in 56 patients. Normal karyotype was identified in 31 (54.4%) patients. Other 25 patients had different chromosomal aberrations including complex karyotype in 8 patients. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes.
Results
The frequency of aberrant methylation was next: SFRP1 68.4%, p15INK4b 63.2%, SOX7 47.4%, SFRP4 42.1%, SFRP5 35.1%. Absence of aberrant methylation was found in 5 (8.8%) patients. The most frequent finding was methylation of 2 and 3 genes simultaneously: 29.8% and 21.1% accordingly. Half of the patients with aberrant methylation status of all 5 studied genes had AML with dysplasia. The most part of patients with complex karyotype (62.5%) had aberrant methylation of 3-5 genes. The difference in the number of patients with complex or normal karyotype who had aberrant methylation of all 5 studied genes was significant: 50.0% vs 9.7% OR=9.3 95% CI 1.5-58.0; p=0.022. The patients with normal karyotype and without FLT3 and NPM1 mutations were separated according to the number of genes with aberrant methylation: 0-2 vs 3-5. There was no significant difference in overall and relapse free survival between these groups.
Conclusion
Aberrant methylation of SOX7, p15INK4b and Wnt pathway antagonist genes is recurrent biologic phenomenon in AML patients. More often this finding occurs in AML patients with myelodysplasia and complex karyotype.
Session topic: E-poster
Type: Publication Only
Background
Aberrant methylation of CpG islands of tumor-supressor genes may be involved in the development of acute myeloid leukemia (AML) and be associated with the natural history of the disease.
Aims
To reveal the features of aberrant methylation of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes in AML patients.
Methods
The data of 57 AML patients with median age of 51.0 years were analyzed. Next AML variants were diagnosed: 2 patients with M0, 7 M1, 23 M2, 4 M4, 8 M5, 3 M6 and 10 with myelodysplasia. Cytogenetic data were available in 56 patients. Normal karyotype was identified in 31 (54.4%) patients. Other 25 patients had different chromosomal aberrations including complex karyotype in 8 patients. Methylation-specific PCR was used to study the methylation status of promoter regions of SOX7, p15INK4b and Wnt pathway antagonist genes.
Results
The frequency of aberrant methylation was next: SFRP1 68.4%, p15INK4b 63.2%, SOX7 47.4%, SFRP4 42.1%, SFRP5 35.1%. Absence of aberrant methylation was found in 5 (8.8%) patients. The most frequent finding was methylation of 2 and 3 genes simultaneously: 29.8% and 21.1% accordingly. Half of the patients with aberrant methylation status of all 5 studied genes had AML with dysplasia. The most part of patients with complex karyotype (62.5%) had aberrant methylation of 3-5 genes. The difference in the number of patients with complex or normal karyotype who had aberrant methylation of all 5 studied genes was significant: 50.0% vs 9.7% OR=9.3 95% CI 1.5-58.0; p=0.022. The patients with normal karyotype and without FLT3 and NPM1 mutations were separated according to the number of genes with aberrant methylation: 0-2 vs 3-5. There was no significant difference in overall and relapse free survival between these groups.
Conclusion
Aberrant methylation of SOX7, p15INK4b and Wnt pathway antagonist genes is recurrent biologic phenomenon in AML patients. More often this finding occurs in AML patients with myelodysplasia and complex karyotype.
Session topic: E-poster
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