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Vol. 12 No. 05 (2025)
International Multidisciplinary Journal for Research & Development

Articles

MOLECULAR AND GENETIC RISK FACTORS FOR THE DEVELOPMENT OF THROMBOTIC AND HEMORRHAGIC COMPLICATIONS IN ESENTIAL THROMBOCYTHEMIA

Published 2025-05-05

  • Musashaykhova Sh. M., Musashaykhov U. Kh.

Musashaykhova Sh. M., Musashaykhov U. Kh.
Andijan State Medical Institute.

Abstract

Essential thrombocythemia (ET) is a pathology of clonal hematopoietic stem cells that leads to increased platelet production. Pathogenetically, ET is a bone marrow disease in which megakaryocyte proliferation leads to persistent hyperthrombocytosis with the risk of vascular thrombosis and thromboembolism. The etiology of the disease has not yet been established. The leading hypothesis is the polyethological nature of the disease occurrence, where the predisposition to the disease is realized under the influence of external factors that damage the genome of a normal cell and lead to its malignant transformation

Molecular genetic analysis of JAK2V617F, JAK2 exon12, MPLW515K/L, and CALR mutations plays an exceptional role in the diagnosis of classic Ph-negative MPN. However, genes that control signal transmission within the cell, chromatin remodeling, DNA methylation, oncogenes, and tumor suppressors are involved in the development of these diseases. Current knowledge suggests that the JAK2V617F mutation may not be the first event in the complex pathogenesis of myeloproliferative diseases (MPD). This review describes the current understanding of molecular genetic disorders that are risk factors and affect the development of thrombotic and hemorrhagic complications in ET.

Keywords

chronic myeloproliferative diseases, essential plateletмformation, primary myelofibrosis, JAK2 gene , MPL gene, CALR gene, triple-negative status.

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References

  1. Abdulkadyrov K. M. Klinicheskaya gematologiya: spravochnik [Clinical hematology: handbook].
  2. - 447 p.
  3. Abdulkadyrov K. M., Shuvaev V. A., Martynkevich I. S. Myeloproliferative neoplasms, Moscow: Litterra, 2016. [Abdulkadyrov K..M., Shuvaev V..A., Martynkevich I..S.. Myeloproliferative neoplasms. Moscow: Litterra, 2016 (In Russ.)].
  4. Vorob'ev A. I. Rukovodstvo po gematologii [Guide to Hematology], ed. by A. I. Vorob'ev, Moscow: Newdiamed, 2007, 1275 p.
  5. Zhernyakova A. A., Martynkevich I. S., Shuvaev V. A. Molecular genetic markers and features of the course of essential thrombocythemia. Fundamental research and Clinical Practice-2017. - Vol. 10, No. 3. - pp. 402-408.
  6. Zhernyakova A. A., Martynkevich I. S., Shuvaev V. A. risk factors for the development of thrombotic and hemorogic complications in essential thrombocythemia. -2017. - Vol. 12, No. 2. - pp. 30-38.
  7. Melikyan A. L., Turkina A. G., Abdulkadyrov K. M. et al. Clinical guidelines for the diagnosis and treatment of Ph-negative myeloproliferative diseases (true polycythemia, essential thrombocythemia, primary myelofibrosis). II Congress of Hematologists (April 2014). Moscow, 2014.
  8. Akpinar T.S., Hancer VS, Nalcaci M, Diz-Kucukkaya R. MPL W515L/K Mutations in chronic myeloproliferative neoplasms. Turk J Haematol. 2013;30(1):8– 12. doi: 10.4274/tjh.65807.
  9. Alvarez-Larran, A. Essential Thrombocythemia in Young Individuals: Frequency and Risk Factors for Vascular Events and Evolution to Myelofibrosis in 126 Patients / A. Alvarez-Larran, F. Cervantes, B. Bellosillo et al // ASH Annual Meeting Abstracts. — 2006. — Vol. 108 № 11. — P. 3598.
  10. Andrikovics H, Krahling T, Balassa K, et al. Distinct clinical characteristics of myeloproliferative neoplasms with calreticulin mutations. Haematologica. 2014;99(7):1184–90. doi: 10.3324/haematol.2014.107482.
  11. Barosi, G. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference / G. Barosi, G. Birgegard, G. Finazzi et al // Blood. — 2009. — Vol. 113 № 20. — P. 4829–4833.
  12. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations
  13. from European LeukemiaNet. J Clin Oncol. 2011;29(6):761–70. doi: 10.1200/jco.2010.31.8436.
  14. Beer P.A., Campbell P.J., Scott L.M., et al. MPL mutations in myeloproliferativedisorders: analysis of the PT-1 cohort. Blood. 2008;112(1):141–9. doi: 10.1182/blood-2008-01-131664.
  15. Beer, P A. How I treat essential thrombocythemia / P. A. Beer, W. N. Erber, P. J. Campbell, A. R. Green // Blood. — 2011. — Vol. 117 № 5. — P. 1472–1482.
  16. Bertozzi I., Peroni E., Coltro G. et al. Thrombotic risk correlates with mutational status in true-essential thrombocythemia. Eur J Clin Invest 2016;46(8):683–9. DOI: 10.1111/eci.12647. PMID: 27271054.
  17. Broseus J, Park J.H., Carillo S, et al. Presence of calreticulin mutations in JAK2-negative polycythemia vera. Blood. 2014;124(26):3964–6. doi: 10.1182/ blood-2014-06-583161.
  18. Campbell, P. J. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study / P. J. Campbell, L. M. Scott, G. Buck t al // The Lancet. — 2005. — Vol. 366 № 9501. — P. 1945–1953.
  19. Campregher P.V., Santos F.P., Perini G.F., Hamerschlak N. Molecular biology of Philadelphia-negative myeloproliferative neoplasms. Rev Bras Hematol Hemoter. 2012;34(2):150–5. doi: 10.5581/1516-8484.20120035.
  20. Chou F.S., Mulloy J.C. The thrombopoietin/MPL pathway in hematopoiesis and leukemogenesis. J Cell Biochem. 2011;112(6):1491-8. doi: 10.1002/ jcb.23089.
  21. Common Terminology Criteria for Adverse Events v4.0 (CTCAE). NIH Publication No. 09–5410. — Publish Date: 2009 May 28. — 180 p.

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