The DNA methyl-transferase 3A gene (DNMT3A) is the third most frequently mutated gene in cytogenetically normal acute myeloid leukemia (CN-AML) patients (20-30 %), who belong to a group of patients with intermediate risk. About 60 % of mutations in this gene have been identified in the arginine codon R882. To date, there is no consensus on whether these mutations can be used as biomarkers for monitoring of minimal residual disease and management of preemptive AML therapy. We studied the occurrence of mutations in the DNMT3A gene in our cohort of patients and their persistence during AML treatment. Using next-generation sequencing, we identified four mutations in 11/25 of our analyzed patients--frequent R882C and R882H mutations, rare Y735S mutation, and a novel L347P mutation. Mutation R882C was detected in 5/11, R882H in 4/11 patients, and Y735S and L347P in one patient each. In 4/7 patients initially carrying mutations in the R882 codon, we found the persistence of mutations also during complete remission with, however, no correlation to AML kinetics. Our findings suggest that mutations in the DNMT3A gene can only be used as a biomarker for those AML patients in whom DNMT3A mutation is lost after therapy.
- MeSH
- akutní myeloidní leukemie genetika MeSH
- DNA-(cytosin-5-)methyltransferasa genetika MeSH
- dospělí MeSH
- kodon genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- missense mutace * MeSH
- monitorování fyziologických funkcí * MeSH
- nádorové biomarkery genetika MeSH
- nádorové proteiny genetika MeSH
- reziduální nádor MeSH
- senioři MeSH
- substituce aminokyselin MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- bcr-abl fúzní proteiny genetika MeSH
- chronická myeloidní leukemie genetika MeSH
- kodon MeSH
- lidé MeSH
- mutace * MeSH
- prospektivní studie MeSH
- substituce aminokyselin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
