ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2019.65.27ymj-861Research ArticleНАУЧНЫЕ ОБЗОРЫ И ЛЕКЦИИSCIENTIFIC REVIEWS AND LECTURESГенетическая гетерогенность Ph-негативных хронических миелопролиферативных заболеванийGenetic heterogeneity of Ph-negative chronic myeloproliferative diseasesАлександроваТ. Н.AleksandrovaT. N.

Александрова Туйара Никоновна – м.н.с., врач гематолог КЦ ГАУ РС(Я) РБ№1 НЦМ

Aleksandrova Tuiara Nikonovna – junior researcher of the laboratory of heritable pathology alexandrova

alexandrova_tuyara@mail.ruПавловаН. И.PavlovaN. I.

Павлова Надежда Ивановна – к.б.н., в.н.с.

Pavlova Nadezhda Ivanovna – PhD, temporary acting chief scientifc offcer - head of the laboratory of heritable pathology

solnishko_84@inbox.ruКуртановХ. А.KurtanovKh. A.

Куртанов Харитон Алексеевич – к.м.н., гл.н.с.- руковод. Отдела

Kurtanov Khariton Alekseevich – PhD, Chief Scientifc Offcer - Head of the Department of Molecular Genetics. Tel.: +7 (914) 106 00 30

hariton_kurtanov@mail.ruМулинаИ. И.MulinaI. I.

Мулина Инна Ивановна – гл. внешт. Гематолог;

зав. отд. Гематологии

Mulina Inna Ivanovna – Head of the Department of hematology National Centre of Medicine

ЯдрихинскаяВ. Н.YadrikhinskayaV. N.

Ядрихинская Вера Николаевна – к.м.н., доцент

Yadrikhinskaya Vera Nikolaevna – candidate of medical sciences, associate professor of department «Hospital therapy, professional diseases, clinical pharmacology»

ЯНЦ КМПRussian FederationМЗ РС(Я); КЦ ГАУ РС(Я) РБ№1 НЦМRussian FederationМИ СВФУ им. М.К. АммосоваРоссияMedical Institute of North-Eastern Federal UniversityRussian Federation201916082025018891Copyright © Александрова Т.Н., Павлова Н.И., Куртанов Х.А., Мулина И.И., Ядрихинская В.Н., 20252025Александрова Т.Н., Павлова Н.И., Куртанов Х.А., Мулина И.И., Ядрихинская В.Н.Aleksandrova T.N., Pavlova N.I., Kurtanov K.A., Mulina I.I., Yadrikhinskaya V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/861

В статье представлен обзор литературы, где описываются современные представления о молекулярной биологии хронических миелопролиферативных заболеваний.

The paper presents a review, which demonstrates current understanding of the molecular biology of chronic myeloproliferative diseases.

хронические миелопролиферативные заболеванияJAK2MPLCALRchronic myeloproliferative diseasesJAK2MPLCALRReferencesИстинная полицитемия: обзор литературы и собственные данные / И.Н. Суборцева, Т.И. Колейникова, Е.И. Пустовая [и др.] // Клиническая онкогематология. – 2015. – Т.8. – №4. – С.397-412.Polycythemia Vera: literature review and own data / I.N. Subortseva, T.J. Kolosheinova, E.J. Pustovaya [et al] // Clinical oncohematology. – 2015. – V.8, №4. – р.397-412.Меликян А.Л. Биология миелопролиферативных заболеваний / А.Л. Меликян, И.н. Суборцева // Клиническая онкогематология. – 2016. – Т.9, №3. – С.314-325. doi: 10.21320/2500-2139-2016-9-3-314-325.Melikyan A.L. Biology of myeloproliferative malignancies / A.L. Melikyan, I.N. Subortseva // Clinical oncohematology. – V.9, №3. – р.314-325. doi: 10.21320/2500-2139-2016-9-3-314-325.Модели миелофиброза (обзор литературы и собственные данные) / А.А. Силютина, И.И. Гин, Н.М. Матюхина [и др.] // Клиническая онкогематология. – 2017. – Т.10, №1. – С.75-84. doi: 10.21320/2500-2139-2017-10-1-75-84.Myelofibrosis models: literature review and own data / A.A. Silyutina, I.I. Gin, N.M. Matyukhina [et al.] // Clinical oncohematology. – 2017. – V.10, №1. – р.75-84. doi: 10.21320/2500-2139-2017-10-1-75-84.Молекулярно-генетические маркеры и особенности течения эссенциальной тромбоцитемии / А.А. Жернякова, И.С. Мартынкевич, В.А. Шуваев [и др.] // Клиническая онкогематология. – 2017. – Т.10, №3. – С.402-408. doi: 10.21320/2500-2139-2017-10-3-402-408.Molecular Genetic Markers and Clinical Characteristics of Essential Thrombocythemia / A.A. Shernyakova, I.S. Masrtynkevich, V.A. Shuvaev [et al.] // Clinical oncohematology. – 2017. – V.10, №3. – P.402-408. doi: 10.21320/2500-2139-2017-10-3-402-408.Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders / EJ Baxter, LM Scott, PJ Campbell // Lancet. – 2005. – V.365, №.9464. – р.1054-1061. doi. org/10.1016/S0140-6736 (05)71142-9.Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders / EJ Baxter, LM Scott, PJ Campbell // Lancet. – 2005. – V.365, №.9464. – р.1054-1061. doi. org/10.1016/S0140-6736 (05)71142-9.Allelic expression imbalance of JAK2V617F mutation in BCR-ABL negative myeloproliferative neoplasms / HR Kim, HJ Choi, YK Kim [et al.]// PLoS one. – 2012. – V.8, №1. - e52518. doi: doi. org/10.1371/journal.pone.0052518.Allelic expression imbalance of JAK2V617F mutation in BCR-ABL negative myeloproliferative neoplasms / HR Kim, HJ Choi, YK Kim [et al.]// PLoS one. – 2012. – V.8, №1. - e52518. doi: doi. org/10.1371/journal.pone.0052518.CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles / R Zini, P Guglielmelli, D Pietra [et al.] // Blood Cancer Journal. – 2017. – V.7, №12. – P.638. doi: 10.1038/s41408-017-0010-2.CALR mutational status identifies different disease subtypes of essential thrombocythemia showing distinct expression profiles / R Zini, P Guglielmelli, D Pietra [et al.] // Blood Cancer Journal. – 2017. – V.7, №12. – P.638. doi: 10.1038/s41408-017-0010-2.Chao MP. Two faces of ET: CALR and JAK2 / MP Chao, J Gotlib // Blood. – 2014. – V.123, №10. – р.1438-1440. doi: https://doi.org/10.1182/blood-2014-01-547596Chao MP. Two faces of ET: CALR and JAK2 / MP Chao, J Gotlib // Blood. – 2014. – V.123, №10. – р.1438-1440. doi: https://doi.org/10.1182/blood-2014-01-547596Сlinical effect of driver mutations of JAK2, CALR and MPL in myelofibrosis / E Rumi, D Pietra, C Pascutto [et al.] // Blood. – 2014. – V.124, №7. – р.1062-1069. doi: 10.1182/blood-2014-05-578435.Сlinical effect of driver mutations of JAK2, CALR and MPL in myelofibrosis / E Rumi, D Pietra, C Pascutto [et al.] // Blood. – 2014. – V.124, №7. – р.1062-1069. doi: 10.1182/blood-2014-05-578435.De Freitas RM. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview / RM De Freitas, CM da Costa Maranduba // Revista Brasileira de Hematologia e Hemoterapia. – 2015. – V.37, №5. – р.348-353. doi:10.1016/j.bjhh.2014.10.001.De Freitas RM. Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview / RM De Freitas, CM da Costa Maranduba // Revista Brasileira de Hematologia e Hemoterapia. – 2015. – V.37, №5. – р.348-353. doi:10.1016/j.bjhh.2014.10.001.Familial MPN predisposition / T Tashi, S Swierczek, JT Prchal // Current hematologic malignancy reports. – 2017. – V.12, №5. – P.442-447. doi: 10.1007/s11899-017-0414-x.Familial MPN predisposition / T Tashi, S Swierczek, JT Prchal // Current hematologic malignancy reports. – 2017. – V.12, №5. – P.442-447. doi: 10.1007/s11899-017-0414-x.High frequency of JAK2 exon 12 mutations in Korean patients with polycythemia vera: novel mutations and clinical significance / CH Park, KO Lee, JH Jang // Journal of clinical pathology. – 2016. – V.69, №8. – P.737-741. doi: 10.1136/jclinpath-2016-203649.High frequency of JAK2 exon 12 mutations in Korean patients with polycythemia vera: novel mutations and clinical significance / CH Park, KO Lee, JH Jang // Journal of clinical pathology. – 2016. – V.69, №8. – P.737-741. doi: 10.1136/jclinpath-2016-203649.JAK2 Allele Burden in the Myeloproliferative Neoplasms: Effects on Phenotype, Prognosis and Change with Treatment / AM Vannucchi, L Pierri, P Guglielmelli // Therapeutic advances in hematology. – 2011. – V.2, №.1. – р.21-32. doi: 10.1177/2040620710394474.JAK2 Allele Burden in the Myeloproliferative Neoplasms: Effects on Phenotype, Prognosis and Change with Treatment / AM Vannucchi, L Pierri, P Guglielmelli // Therapeutic advances in hematology. – 2011. – V.2, №.1. – р.21-32. doi: 10.1177/2040620710394474.JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis / С Lacout, DF Pisani, M Tulliez [et al] // Blood. – 2006. – Vol.108, №5. – P.1652–1660. doi: 10.1182/blood-2006-02-002030.JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis / С Lacout, DF Pisani, M Tulliez [et al] // Blood. – 2006. – Vol.108, №5. – P.1652–1660. doi: 10.1182/blood-2006-02-002030.JAK2V617F monitoring in PV and essential thrombocytemia: clinical usefulness for predicting myelofibrotic transformation and thrombotic events / A Alvarez-Larran, B Bellosillo, A Pereira [et al.] // American Journal of Hematology. – 2014. – V.89, №5. – р.517-523. doi: 10.1002/ajh.23676.JAK2V617F monitoring in PV and essential thrombocytemia: clinical usefulness for predicting myelofibrotic transformation and thrombotic events / A Alvarez-Larran, B Bellosillo, A Pereira [et al.] // American Journal of Hematology. – 2014. – V.89, №5. – р.517-523. doi: 10.1002/ajh.23676.JAK2 or CALR mutation status defines subtypes of ET with substantially different clinical course / E Rumi, D Pietra, V Ferretti [et al.] // Blood. – 2014. – V.123, №10. – р.1544-1551. doi: 10.1182/blood-2013-11-539098.JAK2 or CALR mutation status defines subtypes of ET with substantially different clinical course / E Rumi, D Pietra, V Ferretti [et al.] // Blood. – 2014. – V.123, №10. – р.1544-1551. doi: 10.1182/blood-2013-11-539098.Jones AV. Inherited predisposition to myeloproliferative neoplasms / AV Jones, N Cross CP // Therapeutic advances in hematology. – 2013. – V.4, №4. – P.237-253. doi: 10.1177/2040620713489144.Jones AV. Inherited predisposition to myeloproliferative neoplasms / AV Jones, N Cross CP // Therapeutic advances in hematology. – 2013. – V.4, №4. – P.237-253. doi: 10.1177/2040620713489144.Long-term survival and blast transformation in molecularly-annotated essential thrombocythemia, polycythemia vera and myelofibrosis / A Tefferi, P Guglielmelli, DR Larson [et al] // Blood. – 2014. – V.124, №16. – P.2507-2513. doi: 10.1182/blood-2014-05-579136.Long-term survival and blast transformation in molecularly-annotated essential thrombocythemia, polycythemia vera and myelofibrosis / A Tefferi, P Guglielmelli, DR Larson [et al] // Blood. – 2014. – V.124, №16. – P.2507-2513. doi: 10.1182/blood-2014-05-579136.Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations / F Passamonti, C Elena, S Schnittger [et al.] // Blood. – 2011. – V.117, №10. – P.2813-2816. doi: 10.1182/blood-2010-11-316810Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations / F Passamonti, C Elena, S Schnittger [et al.] // Blood. – 2011. – V.117, №10. – P.2813-2816. doi: 10.1182/blood-2010-11-316810Molecular diagnostics of myeloproliferative neoplasms / SE Langabeer, H Andrikovics, J Asp [et al.] // European journal of haematology. – 2015. – V.95, №9. – P.270-279. doi: 10.1111/ejh.12578.Molecular diagnostics of myeloproliferative neoplasms / SE Langabeer, H Andrikovics, J Asp [et al.] // European journal of haematology. – 2015. – V.95, №9. – P.270-279. doi: 10.1111/ejh.12578.MPL mutations and palpable splenomegaly are independent risk factors for fibrotic progression in ET / M Haider, YC Elala, N Gangat [et al.] // Blood cancer journal. – 2016. – V.10, №6. – P.487. doi: 10.1038/bcj.2016.98.MPL mutations and palpable splenomegaly are independent risk factors for fibrotic progression in ET / M Haider, YC Elala, N Gangat [et al.] // Blood cancer journal. – 2016. – V.10, №6. – P.487. doi: 10.1038/bcj.2016.98.Mutation status of ET and PMF defines clinical outcome / L Asp, B Andreasson, U Hansson [et al.] // Haematologica. – 2016. – V.101, №4. – P.129-132. doi: 10.3324/haematol.2015.138958.Mutation status of ET and PMF defines clinical outcome / L Asp, B Andreasson, U Hansson [et al.] // Haematologica. – 2016. – V.101, №4. – P.129-132. doi: 10.3324/haematol.2015.138958.Pathogenesis of myeloproliferative neoplasms / RC Skoda, A Duek, J Grisouard // Experimental hematology. – 2015. – V.43, №8. – P.599-608 doi: 10.1016/j.exphem.2015.06.007.Pathogenesis of myeloproliferative neoplasms / RC Skoda, A Duek, J Grisouard // Experimental hematology. – 2015. – V.43, №8. – P.599-608 doi: 10.1016/j.exphem.2015.06.007.Scott LM. The JAK2 exon 12 mutations: a comprehensive review / LM Scott // American Journal of Hematology. – 2011. – V.86, №8. – р.668-676. https://doi.org/10.1002/ajh.22063.Scott LM. The JAK2 exon 12 mutations: a comprehensive review / LM Scott // American Journal of Hematology. – 2011. – V.86, №8. – р.668-676. https://doi.org/10.1002/ajh.22063.Shammo JM. Mutations in MPNs: prognostic implications, window to biology, and impact on treatment decisions / JM Shammo, BL Stein // American Society of Hematology Education Program book Education Program book. – 2016. – №1. – P.552-560/ doi:10.1182/asheducation-2016.1.552.Shammo JM. Mutations in MPNs: prognostic implications, window to biology, and impact on treatment decisions / JM Shammo, BL Stein // American Society of Hematology Education Program book Education Program book. – 2016. – №1. – P.552-560/ doi:10.1182/asheducation-2016.1.552.Silvennoinen O. Molecular insights into regulation of JAK2 in myeloproliferative neoplasms / O Silvennoinen, SR Hubbard // Blood. – 2015. – V.125, №22. – P.3388-3392. doi: 10.1182/blood-2015-01-621110.Silvennoinen O. Molecular insights into regulation of JAK2 in myeloproliferative neoplasms / O Silvennoinen, SR Hubbard // Blood. – 2015. – V.125, №22. – P.3388-3392. doi: 10.1182/blood-2015-01-621110.Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2 / J Nangalia, CE Massie, EJ Baxter [et al.] // The New England journal of medicine. – 2013. – V.369, №25. – P.2391-2405. doi: 10.1056/NEJMoa1312542.Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2 / J Nangalia, CE Massie, EJ Baxter [et al.] // The New England journal of medicine. – 2013. – V.369, №25. – P.2391-2405. doi: 10.1056/NEJMoa1312542.The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random? / L Anelli, A Zagaria, G Specchia [et al.] // International journal of molecular sciences. – 2018 - V.19, №4. – 1152. doi: 10.3390/ijms19041152The JAK2 GGCC (46/1) Haplotype in Myeloproliferative Neoplasms: Causal or Random? / L Anelli, A Zagaria, G Specchia [et al.] // International journal of molecular sciences. – 2018 - V.19, №4. – 1152. doi: 10.3390/ijms19041152Them NC. Genetic basis of MPN: Beyond JAK2-V617F / NC Them, R Kralovic // Current hematologic malignancy reports. – 2013. – V.8, №4. – P.299-306. doi: 10.1007/s11899-013-0184-z.Them NC. Genetic basis of MPN: Beyond JAK2-V617F / NC Them, R Kralovic // Current hematologic malignancy reports. – 2013. – V.8, №4. – P.299-306. doi: 10.1007/s11899-013-0184-z.

The authors declare that there are no conflicts of interest present.