Site search
Correspondence address
310 Mira Street, Stavropol, Russia, 355017
Tel
+7 865 2352511, +7 865 2353229.
E-mail
medvestnik@stgmu.ru
The journal is included into The list of leading scientific periodicals.
The journal is included into VINITI database and is registered in Electronic scientific library.
The journal is indexed by SCOPUS, Ulrich's International Periodicals Directory.
[Original research]
Alexander Vladimirovich Vinogradov; Alexey Vasilievich Rezaykin; Sergey Vladimirovich Sazonov; Alexander Grigorievich Sergeev; Marina Yurievna Kapitonova;
The spectrum of ASXL1, FLT3, KIT, NPM1, NRAS, TP53 and WT1 genes mutations was studied in 55 middle aged patients (pts) with acute myeloid leukemia (AML) treated in hematological department since 2008 till 2018. Morphology of AML according to FAB-classification was as follows: M0 – 2, M1 – 3, M2 – 21, М3 – 9, M4 – 13, M4eo – 1, M5 – 1, M6 – 3, M7 – 1, AHL (myelo/lymphoblastic) – 1. Mutations were detected using automatic direct sequencing technique. The frequency of mutations in investigated proto- and antioncogenes was 36.7 %, including 2 cases (25.0 %) with favorable cytogenetics, 7 cases (23.8 %) with unfavorable cytogenetics, 9 cases (22.2 %) with normal karyotype and 2 cases (14.3 %) with unspecified cytogenetics. The frequency of mutations in NPM1 gene exons 9–12 was 22.9 %, NRAS gene exons 1–4 – 12.5 %, FLT3 gene exons 12–15 and 19–21 – 11.5 %, ASXL1 gene exons 12–13 – 11.1 %, KIT gene exons 7–12 and 16–19 – 6.5 %, WT1 gene exons 6–9 – 6.1 %, TP53 gene exons 4–11 – 2.6 %. Multiple genetic lesions were detected in 10.9 % specimens (usually NPM1 and FLT3 point mutations co-occurrence). As a result, detection of cryptic gene mutations was helped to clarify the prognostic stratification of AML in 18.2 % cases. Favorable prognosis of overall survival was established in 9 cases (16.4 %), intermediate – 15 (27.3 %), adverse –19 (34.5 %), unspecified –12 (21.8 %). These results indicate the priority of intensive induction polychemotherapy and allogenic bone marrow transplantation in the first remission as the main therapeutic technology in AML at the age of 45–60 years old.
References:
1. Metzeler K. H., Herold T., Rothenberg-Thurle M., Amler S., Sauerland M. C. [et al.]. Spectrum and prognostic relevance of driver gene mutations in acute myeloid leukemia. Blood. 2016;128(5):686-698. https://doi.org/10.1182/blood-2016-01-693879
2. Shlush L. I., Zandi S., Itzkovitz S., Schuh A. C. Aging, clonal hematopoiesis and preleukemia: not just bad luck? Intern. J. Hematol. 2015;102:513-522. https://doi.org/10.1007/s12185-015-1870-5
3. Abelson S., Collor G., Ng S. W. K., Vassiliou G. S., Shlush L. I. Prediction of acute myeloid leukaemia risk in healthy individuals. Nature. 2018;559(7714):400-404. https://doi.org/10.1038/s41586-018-0317-6
4. Arber D. A., Orazi A., Hasserjian R., Thiele J., Borowitz M. J. [et al.]. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-2405. https://doi.org/10.1182/blood-2016-03-643544
5. Vinogradov A. V., Rezaykin A. V., Salakhov D. R. Sravnitelnyy analiz rezultatov tipirovaniya molekulyarnykh povrezhdeniy gena NPM1 pri ostrykh miyeloidnykh leykozakh s ispolzovaniyem pryamogo avtomaticheskogo sekvenirovaniya i immunogistokhimicheskogo metoda. Vestnik Uralskoy meditsinskoy akademicheskoy nauki. – Bulletin of the Ural Medical Academic Science. 2013;(4):124-127. (In Russ.).
6. Walter R. B., Othus M., Löwenberg B., Erba H. P., Estey E. H. Empiric definition of eligibility criteria for clinical trials in relapsed/refractory acute myeloid leukemia: Analysis of 1.892 patients from HOVON/SAKK and SWOG. Haematologica. 2015;100(10):e409-e411. https://doi.org/10.3324/haematol.2015.130013
7. Vinogradov A. V., Rezaykin A. V., Izotov D. V., Sergeyev A. G. Primeneniye tekhnologii pryamogo avtomaticheskogo sekvenirovaniya dlya detektsii mutatsiy genov ASXL1, DNMT3A, FLT3, KIT, NRAS, TP53 i WT1 pri ostrykh miyeloidnykh leykozakh s neutochnennym kariotipom. Vestnik Uralskoy meditsinskoy akademicheskoy nauki. – Bulletin of the Ural Medical Academic Science. 2016;(4):38-51. (In Russ.).
8. Szatkowski D., Hellmann A. The overexpression of KIT proto-oncogene in acute leukemic cells is not necessarily caused by the gene mutation. Acta Haematologica. 2015;133(1):116-123. https://doi.org/10.1159/000360214
9. Heldin C. H., Lennartsson J. Structural and functional properties of platelet-derived growth factor and stem cell factor receptors. Cold Spring Harbor Perspectives in Biology. 2013;5(8):a009100. https://doi.org/10.1101/cshperspect.a009100
10. Vinogradov A. V., Rezaykin A. V., Sazonov S. V., Sergeyev A. G. Kliniko-patogeneticheskaya kharakteristika mutatsiy genov DNMT3A, FLT3, KIT, NPM1, NRAS, TP53 i WT1 u bolnykh ostrymi miyeloidnymi leykozami v vozrastnoy gruppe 15–45 let. Geny i kletki. – Genes and cells. 2018;14(3):70-74. (In Russ.). https://doi.org/10.22138/2500-0918-2018-15-3-384-392
Keywords: acute myeloid leukemia, mutations, middle age, direct sequencing