The Prognostic Value of Somatic Mutations of Epigenetic Regulation Genes in Acute Myeloid Leukemias in Real-World Clinical Practice: Results of an Observational Non-Interventional Prospective Interregional Study

AUTOIMMUNE THROMBOCYTOPENIA

AA Shatilova1, IG Budaeva1, AV Petukhov1, SA Silonov1, AE Ershova1, TS Nikulina1, YuD Matvienko1, YuV Mirolyubova1, KV Bogdanov1, LV Anchukova2, YuS Neredko3, SYu Tyasko3, OE Ochirova4, AG Karpova4, ER Vasil’eva5, OD Serdyuk6, DA Yaskulskii6, DV Bukin7, YuA Alekseeva1, EG Lomaia1, LL Girshova1

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

2 Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

3 Stavropol Krai Clinical Oncology Dispensary, 182a Oktyabrskaya ul., Stavropol, Russian Federation, 355001

4 NA Semashko Republican Clinical Hospital, 12 Pavlova ul., Ulan-Ude, Russian Federation, 670031

5 Perm Krai Clinical Hospital, 85 Pushkina ul., Perm, Russian Federation, 614990

6 Clinical Oncology Dispensary No. 1, 146 Dimitrova ul., Krasnodar, Russian Federation, 350040

7 Regional Clinical Hospital, 105 Peterburgskoe sh., Tver, Russian Federation, 170036

For correspondence: Aleksina Alekseevna Shatilova, 2 Akkuratova ul., Saint Petersburg, Russian Federation, 197341; Tel.: +7(911)476-35-58; e-mail: alexina-96@list.ru

For citation: Shatilova AA, Budaeva IG, Petukhov AV, et al. The Prognostic Value of Somatic Mutations of Epigenetic Regulation Genes in Acute Myeloid Leukemias in Real-World Clinical Practice: Results of an Observational Non-Interventional Prospective Interregional Study. Clinical oncohematology. 2023;16(2):174–85. (In Russ).

DOI: 10.21320/2500-2139-2023-16-2-174-185

ABSTRACT

Aim. To assess the rate of DNMT3A, IDH1, IDH2, and ASXL1 gene mutations and their effect on the prognosis both as isolated findings and in combination with well-known chromosomal aberrations and gene mutations in newly diagnosed acute myeloid leukemia (AML) patients from some regions of the Russian Federation.

Materials & Methods. The study enrolled 83 patients with newly diagnosed AML from 22 regions of the Russian Federation, who underwent molecular genetic examination for detecting IDH1 (R132), IDH2 (R140), ASXL1, and DNMT3A gene mutations with droplet digital PCR and Sanger sequencing methods.

Results. The mutation rate in DNMT3A was 16.7 %, in IDH1 (R132) it was 6 %, in IDH2 (R140) it was 9.6 %, and in ASXL1 it was 6 %. The R140 mutation in IDH2 correlated with the older age of patients. The mutations in IDH1 (R132), IDH2 (R140), and DNMT3A showed a significant association with mutated NPM1. The mutations in IDH1 (R132), IDH2 (R140) were reported to occur significantly more often in patients with normal karyotype. The IDH1 (R132) and IDH2 (R140) mutations appeared to have a favorable effect on AML prognosis, which is most likely to be associated with a high rate of their compatibility with NPM1 mutation. The mutated type of DNMT3A had a negative effect on overall survival of patients with NPM1 mutation. The mutation in ASXL1 also appeared to be an unfavorable prognostic factor for overall survival of patients with wild type NPM1.

Conclusion. A high rate of mutation occurrence in epigenetic regulation genes as well as the prognostic potential of these mutations in AML necessitate the need for determining the mutation status of DNMT3A, IDH1, IDH2, and ASXL1 in the context of primary diagnosis in real-world clinical practice.

Keywords: acute myeloid leukemias, IDH, DNMT3A, ASXL1, epigenetic regulation genes.

Received: September 25, 2022

Accepted: March 1, 2023

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