Some results of a pilot study of mutations in ASXL1 and DNMT3A genes in myelodysplastic syndrome

Abstract

Оbjective : was to determine the prevalence of the c.1934dupG mutation in the ASXL1 gene and the R882H mutation in the DNMT3A gene in MDS and their influence on significant clinical characteristics. Materials and methods : 33 men and 17 women with a median age of 57 years (18 –83) and a verified diagnosis of myelodysplastic syndrome were included in the study. Twenty-two volunteers without hematologic pathology were taken as controls, of them: 8 men and 14 women aged from 22 to 65 years. PCR examination of venous blood was performed in all study groups to detect c.1934dupG and R882H with Sanger reference sequencing. Results : the R882H mutation was not detected in any of the study groups. The c.1934dupG mutation was not detected in individuals without hematologic pathology. Due to a lack of concentration of isolated DNA from venous blood cells, no analysis of amplification efficiency could be performed in 7 patients. The c.1934dupG mutation was found in 46% of patients and was found in all IPSS-R, WPSS, and MDS-CI risk groups. No differences were found in the analysis of survival in the presence and absence of the c.1934dupG mutation. Conclusions : the study demonstrated that the developed method for the detection of the c.1934dupG mutation in venous blood cells enables optimization of diagnosis. A limitation of the adapted amplification and restriction assays was the degree of blood leucopenia. No effect of the c.1934dupG mutation on the clinical course of myelodysplastic syndrome was detected.