Medical news
of the North Caucasus
Scientific journal
Mass media registration certificate dated December 7, 2006.
Series ПИ #ФС 77-26521.
Federal service for surveillance over non-violation of the legislation in the sphere of mass communications and protection of cultural heritage.
ISSN 2073-8137

Site search

Correspondence address
310 Mira Street, Stavropol, Russia, 355017

+7 865 2352511, +7 865 2353229.


Molecular genetic analisys of c-Kiт gene mutations in acute myeloid leukemia in the age aspect

[Experimental medicine]
Alexander Vladimirovich Vinogradov; Denis Vladimirovich Izotov; Alexey Vasilievich Rezaykin; Sergey Vladimirovich Sazonov; Evgeny Shchetinin; Dmitry Bobryshev; Alexander Grigorievich Sergeev;

Direct automatic sequencing was used to study the oncogenic potential of mutations of the c-Kit gene in exons 7–12 and 16–19 of the gene in 67 patients with newly identified forms of acute myeloid leukemia (AML). Besides, 56 samples were additionally tested for insertion in exon 12 of the NPM1 gene using molecular genetic and immunohistochemical methods. The frequency of functionally significant mutations in the c-Kit gene was 13.4 % (n=9), 5 of which were in the group of AML patients aged 15–45 years (15.2 %), 4 – in elderly patients (11.8 %). That is, the frequency of mutations of the c-Kit gene in patients, depending on age, did not differ statistically significantly. Three samples revealed insertions in the NPM1 gene (5.4 %). However, by computer modeling using Protein Homology/AnalogY Recognition Engine, it was shown that only the missense mutation of с. 2447 A>T, as well as insertions and deletions of exons 10 and 11 (6.0 %, n=4) had oncogenic potential among the detected molecular changes. At the same time, the most common non-synonymous transversion of c. 1621 A>C (7.5 %, n=5), both isolated and combined with the transit of c. 1636 A>G, did not have any significant effect on the structure and did not lead to spontaneous activation of the c-Kit protein. The prognostic impact of detected mutations in the c-Kit gene in AML was unfavorable, but the use of tyrosine kinase inhibitors has clinical prospects along with high-dose chemotherapy and allogeneic bone marrow transplantation.


1. Khwaja A., Bjorkholm M., Gale R. E., Levine R. L, Jordan C. T. [et al.]. Acute myeloid leukemia. Nature Reviews. Disease Primers. 2016;2:16010. https://doi.org/10.1038/nrdp.2016.10
2. 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
3. Long L., Assaraf Y. G., Lei Z. N., Peng H., Yang L. [et al.]. Genetic biomarkers of drug resistance: A compass of prognosis and targeted therapy in acute myeloid leukemia. Drug Resistance Updates. 2020;52:100703. https://doi.org/10.1016/j.drup.2020.100703
4. 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.). https://doi.org/10.22138/2500-0918-2016-14-4-38-51
5. Vinogradov A. V., Rezaykin A. V., Sazonov S. V., Sergeev A. G., Kapitonova M. Yu. Molekulyarno-geneticheskij analiz mutatsij v genakh ASXL1, FLT3, KIT, NPM1, NRAS, TP53 i WT1 u bol’nykh ostrymi mieloidnymi lejkozami zrelogo vozrasta. Meditsinskii vestnik Severnogo Kavkaza. – Medical News of North Caucasus. 2020;15(1):32-36. (In Russ.). https://doi.org/10.14300/mnnc.2020.15006
6. Dufresne A., Alberti L., Brahmi M., Kabani S., Philippon S. [et al.]. Impact of KIT exon 10 M541L allelic variant on the response to imatinib in aggressive fibromatosis: analysis of the desminib series by competitive allele specific Taqman PCR technology. BMC Cancer. 2014;(14):632. https://doi.org/10.1186/1471-2407-14-632
7. Hoade Y., Metzgeroth G., Schwaab J., Reiter A., Cross N. C. P. Routine Screening for KIT M541L Is Not Warranted in the Diagnostic Work-Up of Patients with Hypereosinophilia. Acta Haematology. 2018;139(2):71-73. https://doi.org/10.1159/000485959
8. Laine E., de Beauchene I. C., Perahia D., Auclair C., Tchertanov L. Mutation D816V Alters the Internal Structure and Dynamics of c-Kit Receptor Cytoplasmic Region: Implications for Dimerization and Activation Mechanisms. PLoS Computational Biology. 2011;7(6):e1002068. https://doi.org/10.1371/journal.pcbi.1002068
9. Raghav P. K., Singh A. K., Gangenahalli G. A. Change in Structural Integrity of c-Kit Mutant D816V Causes Constitutive Signaling. Mutation Research. 2018;808:28-38. https://doi.org/10.1016/j.mrfmmm.2018.02.001
10. Babaei M. A., Kamalidehghan B., Saleem M., Huri H. Z., Ahmadipour F. Receptor tyrosine kinase (c-Kit) inhibitors: a potential therapeutic target in cancer cells. Drug Design, Development and Therapy. 2016;(10):2443-2459. https://doi.org/10.2147/DDDT.S89114

Keywords: acute myeloid leukemia, c-Kit gene, young age, old and senile age, sequencing, protein structure modeling

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy