Identification of Mutations in IDH1/2, DNMT3A, ASXL1 Genes of Genome Epigenetic Regulation and Their Co-Occurrence with FLT3, NPM1, RUNX1 Mutations in Acute Myeloid Leukemia

AUTOIMMUNE THROMBOCYTOPENIA ,

EV Belotserkovskaya1,2, EK Zaikova1,2, AV Petukhov1,2,3, ON Demidov2, KA Levchuk1, IG Budaeva1, DV Zaitsev1, YuD Rogovaya1, AA Shatilova1, KV Bogdanov1, YuV Mirolyubova1, TS Nikulina1, AYu Zaritskey1, LL Girshova1

1 VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

2 Institute of Cytology, 4 Tikhoretskii pr-t, Saint Petersburg, Russian Federation, 194064

3 Sirius University of Science and Technology, 1 Olimpiiskii pr-t, Sochi, Russian Federation, 354340

For correspondence: Ekaterina Vasilevna Belotserkovskaya, PhD in Biology, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; e-mail: belotserkovskaya.ev@gmail.com

For citation: Belotserkovskaya EV, Zaikova EK, Petukhov AV, et al. Identification of Mutations in IDH1/2, DNMT3A, ASXL1 Genes of Genome Epigenetic Regulation and Their Co-Occurrence with FLT3, NPM1, RUNX1 Mutations in Acute Myeloid Leukemia. Clinical oncohematology. 2021;14(1):13–21. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-13-21

ABSTRACT

Aim. To identify mutations in IDH1/IDH2, DNMT3A, and ASXL1 genes responsible for genome epigenetic regulation and their co-occurrence with FLT3, NPM1, and RUNX1 mutations in newly diagnosed adult acute myeloid leukemias (AML).

Materials & Methods. The study included 56 patients with newly diagnosed AML treated at the VA Almazov National Medical Research Center. Among them there were 34 men and и 22 women aged 18–76 years (median 46 years). Mutation status of IDH1, IDH2, DNMT3A, and ASXL1 genes of epigenetic regulation was assessed by Sanger sequencing method. Molecular genetic analysis of FLT3, NPM1, and RUNX1-RUNX1T1 genes was performed using commercial kits.

Results. Mutations in epigenetic regulation genes were detected in 14 (25 %) out of 56 patients. Mutation prevalence was not associated with risk groups (p = 0.072). IDH1/2 mutations were identified in 15.6 % of patients and were significantly oftener observed concurrent with NPM1 mutations (62.5 %; p = 0.01) compared to patients with wild-type IDH1/2. In most patients IDH1/2 mutations were associated with normal karyotype (p = 0.002). DNMT3A (R882) mutation was identified in 4 (7.1 %) out of 56 patients within the analyzed group. In 6 patients (11.1 %) ASXL1 mutations were detected co-occurring with RUNX1-RUNX1T1 and FLT3-ITD mutations.

Conclusion. Mutations in epigenetic regulation genes are often identified in AML patients and can be concurrent with abnormalities in NPM1, FLT3 и RUNX1 genes.

Keywords: acute myeloid leukemias, IDH1, IDH2, DNMT3A, and ASXL1 genes of epigenetic regulation, epigenetic factors.

Received: August 20, 2020

Accepted: December 2, 2020

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Статистика Plumx английский

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