Skip to main content
SpringerLink
Log in

JAK2 inhibitors for the treatment of Philadelphia-negative myeloproliferative neoplasms: current status and future directions

  • Comprehensive Review
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

The overactivation of Janus kinases 2 (JAK2) by gain-of-function mutations in the JAK2, Myeloproliferative leukemia virus oncogene, or Calreticulin genes are the most important factor in the development of Philadelphia-negative myeloproliferative neoplasms (MPNs). The discovery of the JAK2V617F mutation is a significant breakthrough in understanding the pathogenesis of MPNs, and inhibition of JAK2 abnormal activation has become one of the most effective strategies against MPNs. Currently, three JAK2 inhibitors for treating MPNs have been approved, and several are being evaluated in clinical trials. However, persistent challenges in terms of drug resistance and off-target effects remain unresolved. In this review, we introduce and classify the available JAK2 inhibitors in terms of their mechanisms and clinical considerations. Additionally, through an analysis of target points, binding modes, and structure–activity inhibitor relationships, we propose strategies such as combination therapy and allosteric inhibitors to overcome specific challenges. This review offers valuable insights into current trends and future directions for optimal management of MPNs using JAK2 inhibitors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Grinfeld J, Nangalia J, Green AR (2017) Molecular determinants of pathogenesis and clinical phenotype in myeloproliferative neoplasms. Haematologica 102:7–17. https://doi.org/10.3324/haematol.2014.113845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Grinfeld J, Nangalia J, Baxter EJ, Wedge DC, Angelopoulos N, Cantrill R et al (2018) Classification and personalized prognosis in myeloproliferative neoplasms. N Engl J Med 379:1416–1430. https://doi.org/10.1056/NEJMoa1716614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Silvennoinen O, Hubbard SR (2015) Molecular insights into regulation of JAK2 in myeloproliferative neoplasms. Blood 125:3388–3392. https://doi.org/10.1182/blood-2015-01-621110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bose P, Masarova L, Verstovsek S (2020) Novel concepts of treatment for patients with myelofibrosis and related neoplasms. Cancers 12:2891. https://doi.org/10.3390/cancers12102891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Esposito MT, So CW (2014) DNA damage accumulation and repair defects in acute myeloid leukemia: implications for pathogenesis, disease progression, and chemotherapy resistance. Chromosoma 123:545–561. https://doi.org/10.1007/s00412-014-0482-9

    Article  CAS  PubMed  Google Scholar 

  6. Samuelson Bannow BT, Salit RB, Storer BE, Stevens EA, Wu D, Yeung C et al (2018) Hematopoietic cell transplantation for myelofibrosis: the dynamic international prognostic scoring system plus risk predicts post-transplant outcomes. Biol Blood Marrow Transplant 24:386–392. https://doi.org/10.1016/j.bbmt.2017.09.016

    Article  PubMed  Google Scholar 

  7. Guglielmelli P, Vannucchi AM (2020) Current management strategies for polycythemia vera and essential thrombocythemia. Blood Rev 42:100714. https://doi.org/10.1016/j.blre.2020.100714

    Article  CAS  PubMed  Google Scholar 

  8. Tefferi A (2018) Primary myelofibrosis: 2019 update on diagnosis, risk-stratification and management. Am J Hematol 93:1551–1560. https://doi.org/10.1002/ajh.25230

    Article  PubMed  Google Scholar 

  9. McMullin MF, Harrison CN, Ali S, Cargo C, Chen F, Ewing J et al (2019) A guideline for the diagnosis and management of polycythaemia vera. Br J Haematol 184:176–191. https://doi.org/10.1111/bjh.15648

    Article  PubMed  Google Scholar 

  10. Gangat N, Singh A, Szuber N, Begna K, Elliott M, Wolanskyj-Spinner A et al (2022) Site-specific venous thrombosis in essential thrombocythemia: impact on subsequent vascular events and survival. J Thromb Haemost 20:2439–2443. https://doi.org/10.1111/jth.15834

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Venugopal S, Mascarenhas J (2020) Novel therapeutics in myeloproliferative neoplasms. J Hematol Oncol 13:162. https://doi.org/10.1186/s13045-020-00995-y

    Article  PubMed  PubMed Central  Google Scholar 

  12. Guy A, Bidet A, Ling C, Caumont C, Boureau L, Viallard J-F et al (2021) Novel findings of splenic extramedullary hematopoiesis during primary myelofibrosis, post-essential thrombocythemia, and post-polycythemia vera myelofibrosis. Virchows Arch 479:755–764. https://doi.org/10.1007/s00428-021-03110-9

    Article  CAS  PubMed  Google Scholar 

  13. Takenaka K, Shimoda K, Akashi K (2018) Recent advances in the diagnosis and management of primary myelofibrosis. Korean J Intern Med 33:679–690. https://doi.org/10.3904/kjim.2018.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Santos FP, Tam CS, Kantarjian H, Cortes J, Thomas D, Pollock R et al (2014) Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation. Leuk Lymphoma 55:121–127. https://doi.org/10.3109/10428194.2013.794269

    Article  PubMed  Google Scholar 

  15. Pettit K, Odenike O (2017) Novel therapies for myelofibrosis. Curr Hematol Malig Rep 12:611–624. https://doi.org/10.1007/s11899-017-0403-0

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tefferi A, Pardanani A (2015) Myeloproliferative neoplasms a contemporary review. JAMA Oncol 1:97–105. https://doi.org/10.1001/jamaoncol.2015.89

    Article  PubMed  Google Scholar 

  17. Cervantes F, Pereira A (2012) Prognostication in primary myelofibrosis. Curr Hematol Malig Rep 7:43–49. https://doi.org/10.1007/s11899-011-0102-1

    Article  PubMed  Google Scholar 

  18. Holmström MO, Hasselbalch HC, Andersen MH (2020) Cancer immune therapy for Philadelphia chromosome-negative chronic myeloproliferative neoplasms. Cancers (Basel) 12:1763. https://doi.org/10.3390/cancers12071763

    Article  CAS  PubMed  Google Scholar 

  19. Geyer HL, Mesa RA (2014) Therapy for myeloproliferative neoplasms: when, which agent, and how? Blood 124:3529–3537. https://doi.org/10.1182/blood-2014-05-577635

    Article  CAS  PubMed  Google Scholar 

  20. Greenfield G, McMullin MF, Mills K (2021) Molecular pathogenesis of the myeloproliferative neoplasms. J Hematol Oncol 14:103. https://doi.org/10.1186/s13045-021-01116-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. How J, Hobbs GS, Mullally A (2019) Mutant calreticulin in myeloproliferative neoplasms. Blood 134:2242–2248. https://doi.org/10.1182/blood.2019000622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sawyers C, Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL et al (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3:270. https://doi.org/10.1371/journal.pmed.0030270

    Article  CAS  Google Scholar 

  23. Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE et al (2006) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood 107:176–183. https://doi.org/10.1182/blood-2005-06-2413

    Article  CAS  PubMed  Google Scholar 

  24. Xin P, Xu X, Deng C, Liu S, Wang Y, Zhou X et al (2020) The role of JAK/STAT signaling pathway and its inhibitors in diseases. Int Immunopharmacol 80:106210. https://doi.org/10.1016/j.intimp.2020.106210

    Article  CAS  PubMed  Google Scholar 

  25. Gao Q, Liang X, Shaikh AS, Zang J, Xu W, Zhang Y (2018) JAK/STAT signal transduction: promising attractive targets for immune, inflammatory and hematopoietic diseases. Curr Drug Targets 19:487–500. https://doi.org/10.2174/1389450117666161207163054

    Article  CAS  PubMed  Google Scholar 

  26. Meyer SC, Levine RL (2014) Molecular pathways: molecular basis for sensitivity and resistance to JAK kinase inhibitors. Clin Cancer Res 20:2051–2059. https://doi.org/10.1158/1078-0432.CCR-13-0279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJP et al (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397. https://doi.org/10.1016/j.ccr.2005.03.023

    Article  CAS  PubMed  Google Scholar 

  28. Kralovics R, Passamonti F, Buser AS, Teo S-S, Tiedt R, Passweg JR et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790. https://doi.org/10.1056/NEJMoa051113

    Article  CAS  PubMed  Google Scholar 

  29. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061. https://doi.org/10.1016/s0140-6736(05)71142-9

    Article  CAS  PubMed  Google Scholar 

  30. Fan W, Cao W, Shi J, Gao F, Wang M, Xu L et al (2023) Contributions of bone marrow monocytes/macrophages in myeloproliferative neoplasms with JAK2(V617F) mutation. Ann Hematol 102:1745–1759. https://doi.org/10.1007/s00277-023-05284-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Edahiro Y, Araki M, Komatsu N (2020) Mechanism underlying the development of myeloproliferative neoplasms through mutant calreticulin. Cancer Sci 111:2682–2688. https://doi.org/10.1111/cas.14503

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shires KL, Rust AJ, Harryparsad R, Coburn JA, Gopie RE (2023) JAK2/STAT5 pathway mutation frequencies in South African BCR/ABL negative MPN patients. Hematol Oncol Stem Cell Ther 16:291–302. https://doi.org/10.56875/2589-0646.1064

    Article  CAS  PubMed  Google Scholar 

  33. Yang LPH, Keating GM (2012) Ruxolitinib in the treatment of myelofibrosis. Drugs 72:2117–2127. https://doi.org/10.2165/11209340-000000000-00000

    Article  CAS  PubMed  Google Scholar 

  34. Plosker GL (2015) Ruxolitinib: a review of its use in patients with myelofibrosis. Drugs 75:297–308. https://doi.org/10.1007/s40265-015-0351-8

    Article  CAS  PubMed  Google Scholar 

  35. Ostojic A, Vrhovac R, Verstovsek S (2011) Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol 7:1035–1043. https://doi.org/10.2217/fon.11.81

    Article  CAS  PubMed  Google Scholar 

  36. Holik H, Krečak I, Lucijanić M, Samardžić I, Pilipac D, Ljubičić IV et al (2023) Hip and knee osteoarthritis in patients with chronic myeloproliferative neoplasms: a cross-sectional study. Life (Basel) 13:1388. https://doi.org/10.3390/life13061388

    Article  CAS  PubMed  Google Scholar 

  37. Baghdassarian H, Blackstone SA, Clay OS, Philips R, Matthiasardottir B, Nehrebecky M et al (2023) Variant stat4 and response to ruxolitinib in an autoinflammatory syndrome. N Engl J Med 388:2241–2252. https://doi.org/10.1056/NEJMoa2202318

    Article  CAS  PubMed  Google Scholar 

  38. Neumann T, Schneidewind L, Weigel M, Plis A, Vaizian R, Schmidt CA et al (2019) Ruxolitinib for therapy of graft-versus-host disease. Biomed Res Int. https://doi.org/10.1155/2019/8163780

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chovatiya R, Paller AS (2021) JAK inhibitors in the treatment of atopic dermatitis. J Allergy Clin Immunol 148:927–940. https://doi.org/10.1016/j.jaci.2021.08.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Barraco F, Greil R, Herbrecht R, Schmidt B, Reiter A, Willenbacher W et al (2020) Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis. Br J Haematol 191:764–774. https://doi.org/10.1111/bjh.16729

    Article  CAS  PubMed  Google Scholar 

  41. Talpaz M, Kiladjian JJ (2021) Fedratinib, a newly approved treatment for patients with myeloproliferative neoplasm-associated myelofibrosis. Leukemia 35:1–17. https://doi.org/10.1038/s41375-020-0954-2

    Article  CAS  PubMed  Google Scholar 

  42. Waksal JA, Tremblay D, Mascarenhas J (2021) Clinical utility of fedratinib in myelofibrosis. Onco Targets Ther 14:4509–4521. https://doi.org/10.2147/OTT.S267001

    Article  PubMed  PubMed Central  Google Scholar 

  43. Palmer J, Mesa R (2020) The role of fedratinib for the treatment of patients with primary or secondary myelofibrosis. Ther Adv Hematol. https://doi.org/10.1177/2040620720925201

    Article  PubMed  PubMed Central  Google Scholar 

  44. Duong VH, Komrokji RS (2014) The role of pacritinib in the management of myelofibrosis. Expert Rev Hematol 7:325–332. https://doi.org/10.2217/fon.15.200

    Article  CAS  PubMed  Google Scholar 

  45. Lamb YN (2022) Pacritinib: first approval. Drugs 82:831–838. https://doi.org/10.1007/s40265-022-01718-y

    Article  CAS  PubMed  Google Scholar 

  46. Tremblay D, Mascarenhas J (2018) Pacritinib to treat myelofibrosis patients with thrombocytopenia. Expert Rev Hematol 11:707–714. https://doi.org/10.1080/17474086.2018.1500456

    Article  CAS  PubMed  Google Scholar 

  47. Xu L, Feng J, Gao G, Tang H (2019) Momelotinib for the treatment of myelofibrosis. Expert Opin Pharmacother 20:1943–1951. https://doi.org/10.1080/14656566.2019.1657093

    Article  CAS  PubMed  Google Scholar 

  48. Verstovsek S, Chen C-C, Egyed M, Ellis M, Fox L, Goh YT et al (2021) Momentum: momelotinib vs danazol in patients with myelofibrosis previously treated with JAKi who are symptomatic and anemic. Future Oncol 17:1449–1458. https://doi.org/10.2217/fon-2020-1048

    Article  CAS  PubMed  Google Scholar 

  49. Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC et al (2013) Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J 3:e109. https://doi.org/10.1038/bcj.2013.6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Berdeja J, Palandri F, Baer MR, Quick D, Kiladjian JJ, Martinelli G et al (2018) Phase 2 study of gandotinib (LY2784544) in patients with myeloproliferative neoplasms. Leuk Res 71:82–88. https://doi.org/10.1016/j.leukres.2018.06.014

    Article  CAS  PubMed  Google Scholar 

  51. Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T et al (2011) Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms. Blood Cancer J 1:e29. https://doi.org/10.1038/bcj.2011.29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Liu J, Lv B, Yin H, Zhu X, Wei H, Ding Y (2020) A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple ascending dose and food effect study to evaluate the tolerance, pharmacokinetics of jaktinib, a new selective janus kinase inhibitor in healthy Chinese volunteers. Front Pharmacol 11:604314. https://doi.org/10.3389/fphar.2020.604314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Davis RR, Li B, Yun SY, Chan A, Nareddy P, Gunawan S et al (2021) Structural insights into jak2 inhibition by ruxolitinib, fedratinib, and derivatives Thereof. J Med Chem 64:2228–2241. https://doi.org/10.1021/acs.jmedchem.0c01952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bader MS, Meyer SC (2022) JAK2 in Myeloproliferative neoplasms: still a protagonist. Pharmaceuticals 15:160. https://doi.org/10.3390/ph15020160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hasselbalch HC (2013) The role of cytokines in the initiation and progression of myelofibrosis. Cytokine Growth Factor Rev 24:133–145. https://doi.org/10.1016/j.cytogfr.2013.01.004

    Article  CAS  PubMed  Google Scholar 

  56. Koppikar P, Bhagwat N, Kilpivaara O, Manshouri T, Adli M, Hricik T et al (2012) Heterodimeric JAK-STAT activation as a mechanism of persistence to JAK2 inhibitor therapy. Nature 489:155–159. https://doi.org/10.1038/nature11303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Deshpande A, Reddy MM, Schade GO, Ray A, Chowdary TK, Griffin JD et al (2012) Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia 26:708–715. https://doi.org/10.1038/leu.2011.255

    Article  CAS  PubMed  Google Scholar 

  58. Downes CEJ, McClure BJ, Rehn J, Breen J, Bruning JB, Yeung DT et al (2020) Acquired mutations within the jak2 kinase domain confer resistance to jak inhibitors in an in vitro model of a high-risk acute lymphoblastic leukemia. Blood 136:5–6. https://doi.org/10.1182/blood-2020-133491

    Article  Google Scholar 

  59. Bhagwat N, Levine RL, Koppikar P (2013) Sensitivity and resistance of JAK2 inhibitors to myeloproliferative neoplasms. Int J Hematol 97:695–702. https://doi.org/10.1007/s12185-013-1353-5

    Article  CAS  PubMed  Google Scholar 

  60. Brkic S, Meyer SC (2021) Challenges and perspectives for therapeutic targeting of myeloproliferative neoplasms. Hemasphere. https://doi.org/10.1097/HS9.0000000000000516

    Article  PubMed  Google Scholar 

  61. Khan I, Huang Z, Wen Q, Stankiewicz MJ, Gilles L, Goldenson B et al (2013) AKT is a therapeutic target in myeloproliferative neoplasms. Leukemia 27:1882–1890. https://doi.org/10.1038/leu.2013.167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lu X, Smaill JB, Ding K (2020) New promise and opportunities for allosteric kinase inhibitors. Angew Chem Int Ed Engl 59:13764–13776. https://doi.org/10.1002/anie.201914525

    Article  CAS  PubMed  Google Scholar 

  63. Kung JE, Jura N (2019) Prospects for pharmacological targeting of pseudokinases. Nat Rev Drug Discov 18:501–526. https://doi.org/10.1038/s41573-019-0018-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Byrne DP, Foulkes DM, Eyers PA (2017) Pseudokinases: update on their functions and evaluation as new drug targets. Future Med Chem 9:245–265. https://doi.org/10.4155/fmc-2016-0207

    Article  CAS  PubMed  Google Scholar 

  65. Wu P, Clausen MH, Nielsen TE (2015) Allosteric small-molecule kinase inhibitors. Pharmacol Ther 156:59–68. https://doi.org/10.1016/j.pharmthera.2015.10.002

    Article  CAS  PubMed  Google Scholar 

  66. Wrobleski ST, Moslin R, Lin S, Zhang Y, Spergel S, Kempson J et al (2019) Highly selective inhibition of tyrosine kinase 2 (tyk2) for the treatment of autoimmune diseases: discovery of the allosteric inhibitor BMS-986165. J Med Chem 62:8973–8995. https://doi.org/10.1021/acs.jmedchem.9b00444

    Article  CAS  PubMed  Google Scholar 

  67. Le AM, Puig L, Torres T (2022) Deucravacitinib for the treatment of psoriatic disease. Am J Clin Dermatol 23:813–822. https://doi.org/10.1007/s40257-022-00720-0

    Article  PubMed  PubMed Central  Google Scholar 

  68. Singh J (2022) The ascension of targeted covalent inhibitors. J Med Chem 65:5886–5901. https://doi.org/10.1021/acs.jmedchem.1c02134

    Article  CAS  PubMed  Google Scholar 

  69. Baillie TA (2016) Targeted covalent inhibitors for drug design. Angew Chem Int Ed Engl 55:13408–13421. https://doi.org/10.1002/anie.201601091

    Article  CAS  PubMed  Google Scholar 

  70. Kavanagh ME, Horning BD, Khattri R, Roy N, Lu JP, Whitby LR et al (2022) Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine. Nat Chem Biol 18:1388–1398. https://doi.org/10.1038/s41589-022-01098-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Ishikawa C, Senba M, Mori N (2018) Anti-adult T-cell leukemia/lymphoma activity of cerdulatinib, a dual SYK/JAK kinase inhibitor. Int J Oncol 53:1681–1690. https://doi.org/10.3892/ijo.2018.4513

    Article  CAS  PubMed  Google Scholar 

  72. Shen P, Wang Y, Jia X, Xu P, Qin L, Feng X et al (2022) Dual-target janus kinase (jak) inhibitors: comprehensive review on the JAK-based strategies for treating solid or hematological malignancies and immune-related diseases. Eur J Med Chem 239:114551. https://doi.org/10.1016/j.ejmech.2022.114551

    Article  CAS  PubMed  Google Scholar 

  73. Li X, Li X, Liu F, Li S, Shi D (2021) Rational multitargeted drug design strategy from the perspective of a medicinal chemist. J Med Chem 64:10581–10605. https://doi.org/10.1021/acs.jmedchem.1c00683

    Article  CAS  PubMed  Google Scholar 

  74. Tian XY, Liu L (2012) Drug discovery enters a new era with multi-target intervention strategy. Chin J Integr Med 18:539–542. https://doi.org/10.1007/s11655-011-0900-2

    Article  PubMed  Google Scholar 

  75. Passamonti F, Maffioli M (2018) The role of JAK2 inhibitors in MPNs 7 years after approval. Blood 131:2426–2435. https://doi.org/10.1182/blood-2018-01-791491

    Article  CAS  PubMed  Google Scholar 

  76. Cervantes F, Martinez-Trillos A (2013) Myelofibrosis: an update on current pharmacotherapy and future directions. Expert Opin Pharmacother 14:873–884. https://doi.org/10.1517/14656566.2013.783019

    Article  CAS  PubMed  Google Scholar 

  77. Xu N, Luo J, Luo D, Liang H, Tan Y, Liu Q et al (2021) Targeting metabolic dysregulation for ruxolitinib failure in MPN. Blood 138:4321–4321. https://doi.org/10.1182/blood-2021-150291

    Article  Google Scholar 

  78. Sant’Antonio E, Bonifacio M, Breccia M, Rumi E (2019) A journey through infectious risk associated with ruxolitinib. Br J Haematol 187:286–295. https://doi.org/10.1111/bjh.16174

    Article  PubMed  Google Scholar 

  79. Mascarenhas J, Hoffman R, Talpaz M, Gerds AT, Stein B, Gupta V et al (2018) Pacritinib vs best available therapy, including ruxolitinib, in patients with myelofibrosis: a randomized clinical trial. JAMA Oncol 4:652–659. https://doi.org/10.1001/jamaoncol.2017.5818

    Article  PubMed  PubMed Central  Google Scholar 

  80. Verstovsek S, Talpaz M, Ritchie E, Wadleigh M, Odenike O, Jamieson C et al (2017) A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis. Leukemia 31:393–402. https://doi.org/10.1038/leu.2016.215

    Article  CAS  PubMed  Google Scholar 

  81. Zhang Y, Zhou H, Jiang Z, Wu D, Zhuang J, Li W et al (2022) Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naive patients with myelofibrosis: results of a phase II trial. Am J Hematol 97:1510–1519. https://doi.org/10.1002/ajh.26709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Financial support from Sichuan Science and Technology Program of China (2023NSFSC1692 and 2022YFS0614), and Luzhou Science and Technology Program of China (2022-SYF-46).

Author information

Author notes

  1. Xiaofeng Liu and Binyou Wang have contributed equally to this work.

Authors and Affiliations

  1. School of Basic Medical Sciences, Southwest Medical University, Luzhou, 646000, China

    Xiaofeng Liu, Binyou Wang, Yuan Liu, Yang Yu, Ying Wan, Jianming Wu & Yiwei Wang

  2. Zigong Mental Health Center, Zigong Affiliated Hospital of Southwest Medical University, Zigong, 643000, China

    Binyou Wang, Yang Yu, Jianming Wu & Yiwei Wang

  3. Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China

    Yang Yu, Jianming Wu & Yiwei Wang

  4. Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Southwest Medical University, Luzhou, 646000, China

    Jianming Wu

Authors
  1. Xiaofeng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Binyou Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yang Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Wan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianming Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yiwei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XL, BW and YW wrote the main manuscript text. BW, YY, YL and XL prepared the articles collection. JW and YW supervised and advanced the process. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jianming Wu or Yiwei Wang.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, X., Wang, B., Liu, Y. et al. JAK2 inhibitors for the treatment of Philadelphia-negative myeloproliferative neoplasms: current status and future directions. Mol Divers (2023). https://doi.org/10.1007/s11030-023-10742-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11030-023-10742-3

Keywords

Search

Navigation