А.M. SAVRILOVA¹, I.S. МARTYNKEVICH², L.B. POLUSHKINA², О.Yu. VINOGRADOVA³, А.V. KOSTERINA⁴, М.A. KUNST¹, А. V. BAGAUTDINOV¹

¹Republic Clinical Hospital of the Ministry of Healthcare of the Republic of Tatarstan, Kazan

²Scientific Research Institute of Hematology and Transfusion, Saint- Petersburg

³City Clinical Hospital named after S. P. Botkin, Moscow

⁴Kazan State Medical University of the Ministry of Healthcare of the Russian Federation, Kazan

Contact:

Savrilova A.M. ― hematologist

Address: 138 Orenburgskiy Trakt, 420064, tel. +7-905-312-63-09, e-mail: alsu-mindubaeva@yandex.ru

 Activation of JAK-STAT signaling pathway is the leading cause in pathogenesis of Ph-negative myeloproliferative disorders.  In some cases JAK2 V617F mutation or less common MPL and CALR mutations revealed. Triple negative status occurs if no mutation is confirmed. The article shows incidence and influence of driver mutations (JAK2V617F, MPL, CALR) on clinical picture, prognosis and therapy results in patients with Ph-negative myeloproliferative neoplasms in the Republic of Tatarstan. The research included 128 patients. The most common was JAK2V617F mutation. Triple negative patients showed the worst survival rate. Interferon therapy had advantage in comparison to hydroxycarbamide.

Key words: Ph-negative MPN, JAK2V617F, MPL, CALR, triple negative status, interferon, hydroxycarbamide.

(For citation: Savrilova А.M., Мartynkevich I.S., Polushkina L.B., Vinogradova О.Yu., Kosterina А.V., Kunst М.A., Bagautdinov А.V. Features of Ph-negative myeloproliferative neoplasms with different driver mutations in patients in the Republic of Tatarstan. Practical medicine. 2019. Vol. 17, № 6 (part 1), P. 94-99)

REFERENCES

1. Arber D.A., Orazi A., Hasserjian R. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood, 2016, vol. 127, no. 20, pp. 2391-2405.
2. Rollison D.E., Howlader N., Smith M.T. et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood, 2008, vol. 112, no. 1, pp. 45-52.
3. Tefferi F. The history of myeloproliferative disorders: before and after Dameshek. Leykemia, 2008, no. 22, pp. 3-13.
4. Vannucchi A.M., P. Guglielmelli P. Molecular pathophysiology of Philadelphia-negative myeloproliferative disorders: beyond JAK2 and MPL mutations. Haematologica, 2008, vol. 93, no. 7, pp. 972–976.
5. Vannucchi A.M., Antonioli E., Guglielmelli P., Pardanani A., Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: A critical reappraisal. Leukemia, 2008, no. 22, pp. 1299–1307.
6. Pardanani A., Lasho T.L., Finke C., Hanson C.A., Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia, 2007, no. 21, pp. 1960–1963.
7. Tefferi A. Pathogenesis of myelofibrosis with myeloid metaplasia. J Clin Oncol, 2005, no. 23(33), pp. 8520-30.
8. Tefferi A., Thiele J., Orazi A. et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis: Recommendations from an ad hoc international expert panel. Blood, 2007, no. 110, pp. 1092–1097.
9. Campbell P.J., Scott L.M., Baxter E.J., Bench A.J., Green A.R., Erber W.N. Methods for the detection of the JAK2 V617F mutation in human myeloproliferative disorders. Methods Mol Med, 2006, no. 125, pp. 253-264.
10. Pikman Y., Lee H.H., Mercher T. et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLOS Medicine, 2006, vol. 3, no.7, p. 270.
11. Klampfl, T., Gisslinger H., Harutyunyan A.S. et al. Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms. The New England Journal of Medicine, 2013, vol. 369, no. 25, pp. 2391-2405.
12. Nangalia, J., Massie C.E., Baxter E.J. et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. American Journal of Hematology, 2014, vol. 89, no. 8, pp. 2392-2405.
13. Langabeer S.E., Andrikovics S., Asp J. et al. Molecular diagnostics of myeloproliferative neoplasms. European Journal of Hematology, 2015, vol. 95, no. 47, pp. 270-279.
14. Melikyan A.L., Turkina A.G., Abdulkadyrov K.M., Zaritskiy A.Yu. et al. Klinicheskie rekomendatsii po diagnostiki i terapii Ph-negativnykh mieloproliferativnykh zabolevaniy (istinnaya politsitemiya, essentsial’naya trombotsitemiya, pervichnyy mielofibroz) [Clinical recommendations for the diagnosis and treatment of Ph-negative myeloproliferative diseases (true polycythemia, essential thrombocythemia, primary myelofibrosis)]. Mooscow, 2014. 81 p.
15. Abdulkadyrov K.M., Shuvaev V.A., Martynkevich I.S. Mieloproliferativnye novoobrazovaniya [Myeloproliferative neoplasms]. Moscow: Litterra, 2016. 304 p.