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UkraineOncoGlobal

Журнал «Практическая онкология» Том 5, №1, 2022

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Мієлопроліферативні та лімфопроліферативні захворювання: сьогодення та новітні можливості лікування (огляд літератури)

Авторы: Рудюк Т.О. (1), Новосад О.І. (2)
(1) — Національний медичний університет імені О.О. Богомольця, м. Київ, Україна
(2) — Національний інститут раку, м. Київ, Україна

Рубрики: Онкология

Разделы: Справочник специалиста

Версия для печати


Резюме

Мієлопроліферативні захворювання (МПЗ), що включають істинну поліцитемію (ІП), есенціальну тромбоцитемію (ЕT) і первинний мієлофіброз (ПМФ), є клональними порушеннями, ускладненими в основному судинними проявами і трансформацією в мієлофіброз (для ІП і ET) або лейкоз. Вторинні злоякісні новоутворення, зокрема лімфопроліферативні захворювання (ЛПЗ), зустрічаються значно рідше, однак вони виникають з більшою частотою, ніж у загальній популяції. В даному огляді ми зосередились на трьох питаннях: 1) роль JAK2 і шляхи JAK/STAT у виникненні МПЗ і ЛПЗ; 2) значення генетичної схильності у виникненні як МПЗ, так і ЛПЗ; 3) яке місце займають циторедуктивні препарати у виникненні МПЗ і ЛПЗ.

Myeloproliferative neoplasms (MPN), which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are clonal disorders complicated mainly by vascular events and transformation to myelofibrosis (for polycythemia vera and essential thrombocythemia) or leukemia. Secondary malignancies, particularly lymphoproliferative disorders (LPN), are rare. They occur at a higher frequency than found in the general population. This review focused on three issues: 1) the role of JAK2 and JAK/STAT pathways in the emergence of MPN and LPN; 2) the importance of genetic predisposition in the occurrence of both MPN and LPN; 3) the place of cytoreductive drugs in causing the MPN and LPN.


Ключевые слова

інгібітори JAK; шлях JAK/STAT; JAK2; лімфопроліферативні захворювання; мієлопроліферативні захворювання; руксолітиніб

JAK inhibitors; JAK/STAT pathway; JAK2; lymphoproliferative disorders; myeloproliferative neoplasms; ruxolitinib


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Список литературы

  1. Passamonti F., Rumi E., Pungolino E. et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. The American Journal of Medicine. 2004. 117(10). 755-761. 
  2. JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders. F1000Research. 2018. 7(F1000 Faculty Rev.). 82. Last updated: 17 JAN 2018. 
  3. 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. 127(20). 2391-2405. 
  4. Kralovics R., Passamonti F., Buser A.S. et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. The New England Journal of Medicine. 2005. 352 (17). 1779-1790. 
  5. Pietra D., Li S., Brisci A. et al. Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood. 2008. 111(3). 1686-1689. 
  6. Tasian S.K., Loh M.L., Hunger S.P. Philadelphia chromosome-like acute lymphoblastic leukemia. Blood. 2017. 130(19). 2064-2072. 
  7. Bandaranayake R.M., Ungureanu D., Shan Y., Shaw D.E., Silvennoinen O., Hubbard S.R. Crystal structures of the JAK2 pseudokinase domain and the pathogenic mutant V617F. Nature Structural & Molecular Biology. 2012. 19(8). 754-759. 
  8. Levine R.L., Pardanani A., Tefferi A., Gilliland D.G. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat. Rev. Cancer. 2007. 7(9). 673-683. 
  9. Green M.R., Monti S., Rodig S.J. et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010. 116(17). 3268-3277. 
  10. Dawson M.A., Bannister A.J., Göttgens B. et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009. 461(7265). 819-822. 
  11. Liu F., Zhao X., Perna F. et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell. 2011. 19(2). 283-294. 
  12. Tiacci E., Ladewig E., Schiavoni G. et al. Pervasive mutations of JAK-STAT pathway genes in classical Hodgkin lymphoma. Blood. 2018. 131(22). 2454-2465. 
  13. Mottok A., Hung S.S., Chavez E.A. et al. Integrative genomic analysis identifies key pathogenic mechanisms in primary mediastinal large B-cell lymphoma. Blood. 2019. 134(10). 802-813. 
  14. Meier C., Hoeller S., Bourgau C. et al. Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas. Modern Pathology. 2009. 22(3). 476-487. 
  15. Rui L., Emre N.C., Kruhlak M.J. et al. Cooperative epigenetic modulation by cancer amplicon genes. Cancer Cell. 2010. 18(6). 590-605. 
  16. Van Arnam J.S., Lim M.S., Elenitoba-Johnson K.S.J. Novel insights into the pathogenesis of T-cell lymphomas. Blood. 2018. 131(21). 2320-2330. 
  17. Dufva O., Kankainen M., Kelkka T. et al. Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target. Nature Communications. 2018. 9(1). 1567. 
  18. Kuusanmäki H., Dufva O., Parri E. et al. Drug sensitivity profiling identifies potential therapies for lymphoproliferative disorders with overactive JAK/STAT3 signaling. Oncotarget. 2017. 8(57). 97516-97527. 
  19. Hao Y., Chapuy B., Monti S., Sun H.H., Rodig S.J., Shipp M.A. Selective JAK2 inhibition specifically decreases Hodgkin lymphoma and mediastinal large B-cell lymphoma growth in vitro and in vivo. Clin. Cancer Research. 2014. 20(10). 2674-2683. 
  20. Kim S.J., Kang H.J., Dong-Yeop S. et al. The efficacy of JAK2 inhibitor in heavily pretreated classical hodgkin lymphoma: a prospective pilot study of ruxolitinib in relapsed or refractory classical Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2016. Vol. 128. 1820. 
  21. Van Den Neste E., André M., Gastinne T. et al. A phase II study of the oral JAK1/JAK2 inhibitor ruxolitinib in advanced relapsed/refractory Hodgkin lymphoma. Haematologica. 2018. 103(5). 840-848. 
  22. Landgren O., Goldin L.R., Kristinsson S.Y., Helgadottir E.A., Samuelsson J., Björkholm M. Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11,039 patients with myeloproliferative neoplasms in Sweden. Blood. 2008. 112(6). 2199-2204. 
  23. Jones A.V., Chase A., Silver R.T. et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nature Genetics. 2009. 41(4). 446-449. 
  24. Kilpivaara O., Mukherjee S., Schram A.M. et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat. Genet. 2009. 41(4). 455-459. 
  25. Jones A.V., Campbell P.J., Beer P.A. et al. The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood. 2010. 115(22). 4517-4523. 
  26. Tefferi A., Lasho T.L., Patnaik M.M. et al. JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: Nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival. Leukemia. 2010. 24(1). 105-109. 
  27. Oddsson A., Kristinsson S.Y., Helgason H. et al. The germline sequence variant rs2736100_C in TERT associates with myeloproliferative neoplasms. Leukemia. 2014. 28(6). 1371-1374. 
  28. Jäger R., Harutyunyan A.S., Rumi E. et al. Common germline variation at the TERT locus contributes to familial clustering of myeloproliferative neoplasms. The American Journal of Medicine. 2014. 89(12). 1107-1110. 
  29. Olcaydu D., Rumi E., Harutyunyan A. et al. The role of the JAK2 GGCC haplotype, TET2, and CBL in familial myeloproliferative neoplasms. Haematologica. 2010. 95. 163. 
  30. Harutyunyan A.S., Giambruno R., Krendl C. et al. Germline RBBP6 mutations in familial myeloproliferative neoplasms. Blood. 2016. 127(3). 362-365. 
  31. Olcaydu D., Harutyunyan A., Jäger R. et al. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat. Genet. 2009. 41(4). 450-454.
  32. Frederiksen H., Farkas D.K., Christiansen C.F., Hasselbalch H.C., Sørensen H.T. Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study. Blood. 2011. 118 (25). 6515-6520. 
  33. Hasselbalch H.C., Bjørn M.E. MPNs as inflammatory diseases: the evidence, consequences, and perspectives. Mediators Inflamm. 2015. 2015. 102476. 
  34. Barosi G. An immune dysregulation in MPN. Curr. Hematol. Malig. Rep. 2014. 9(4). 331-339. 
  35. Wang J.C., Kundra A., Andrei M. et al. Myeloid-derived suppressor cells in patients with myeloproliferative neoplasm. Leuk. Res. 2016. 43. 39-43. 
  36. Parampalli Yajnanarayana S., Stübig T., Cornez I. et al. JAK1/2 inhibition impairs T cell function in vitro and in patients with myeloproliferative neoplasms. Br. J. Haematol. 2015. 169(6). 824-833. 
  37. McLornan D.P., Khan A.A., Harrison C.N. Immunological consequences of JAK inhibition: friend or foe? Curr. Hematol. Malig. Rep. 2015. 10(4). 370-379. 
  38. Porpaczy E., Tripolt S., Hoelbl-Kovacic A. et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. Blood. 2018. 132(7). 694-706.
  39. Pemmaraju N., Kantarjian H., Nastoupil L. et al. Characteristics of patients with myeloproliferative neoplasms with lymphoma, with or without JAK inhibitor therapy. Blood. 2019. 133. 2348-2351. 
  40. Rumi E., Zibellini S., Boveri E. et al. Ruxolitinib treatment and risk of B-cell lymphomas in myeloproliferative neoplasms. Am. J. Hematol. 2019. 94(7). E185-E188. 
  41. Rumi E., Zibellini S. JAK inhibitors and risk of B-cell lymphomas. Blood. 2019. 133(21). 2251-2253.
  42. Arcaini L., Cazzola M. Benefits and risks of JAK inhibition. Blood. 2018. 132(7). 675-676.
  43. Maffioli M., Giorgino T., Mora B. et al. Second primary malignancies in ruxolitinib-treated myelofibrosis: real-world evidence from 219 consecutive patients. Blood Adv. 2019. 3(21). 3196-3200.
  44. Cappellini M.D. et al. Sotatercept, a novel transforming growth factor β ligand trap, improves anemia in β-thalassemia: a phase II, open-label, dose-finding study. Red Cell Biology & its Disorders. Haematologica. 2019. Vol. 104(3). 477-484. 
  45. Mascarenhas J., Sandy L., Lu M. et al. A phase II study of panobinostat in patients with primary myelofibrosis (PMF) and post-polycythemia vera/essential thrombocythemia myelofibrosis (post-PV/ET MF). Leuk. Res. 2017. 53. 13-9.
  46. Verstovsek S., Manshouri T., Pilling D. et al. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis. J. Exp. Med. 2016. 213(9). 1723-40.
  47. Stein B.L., Swords R., Hochhaus A. et al. Novel myelofibrosis treatment strategies: potential partners for combination therapies. Leukemia. 2014. 28(11). 2139-47.
  48. Schneider R.K., Mullally A., Dugourd A. et al. Gli1+ Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an Important Cellular Therapeutic Target. Cell. Stem. Cell. 2017. 20(6). 785-800.e8.
  49. Badar T., Kantarjian H.M., Ravandi F. et al. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. Leuk. Res. 2015. 39(9). 950-6.
  50. Quintás-Cardama A., Tong W., Kantarjian H. et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/ polycythemia vera myelofibrosis. Leukemia. 2008. 22(5). 965-70.
  51. Jatiani S.S., Cosenza S.C., Reddy M.V.R. et al. A Non-ATP-Competitive Dual Inhibitor of JAK2 and BCR-ABL Kinases: Elucidation of a Novel Therapeutic Spectrum Based on Substrate Competitive Inhibition. Genes. Cancer. 2010. 1. 331-345. 
  52. Lipka D.B., Hoffmann L.S., Heidel F. et al. LS104, a non-ATP-competitive small-molecule inhibitor of JAK2, is potently inducing apoptosis in JAK2V617F-positive cells. Mol. Cancer Ther. 2008. 7. 1176-1184. 
  53. Zhang J., Adrián F.J., Jahnke W. et al. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010. 463(7280). 501-6. 
  54. Ohren J.F., Chen H., Pavlovsky A. et al. Structures of human MAP kinase kinase 1 (MEK1) and MEK2 describe novel noncompetitive kinase inhibition. Nat. Struct. Mol. Biol. 2004. 11(12). 1192-7.
  55. Ukraine Data on Prognostic Factors and Treatment Outcomes in Patients with Peripheral T-Cell Lymphomas. Klin. Onkol. Fall. 2019. 32(6). 436-444. doi: 10.14735/amko2019436.

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