New Markers of Disease Progression in Myelofibrosis

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Nov 13

PMID 34771488

Citations 7

Authors

Rita Campanelli

Margherita Massa

Vittorio Rosti

Giovanni Barosi

Affiliations

Soon will be listed here.

Abstract

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm due to the clonal proliferation of a hematopoietic stem cell. The vast majority of patients harbor a somatic gain of function mutation either of or or genes in their hematopoietic cells, resulting in the activation of the JAK/STAT pathway. Patients display variable clinical and laboratoristic features, including anemia, thrombocytopenia, splenomegaly, thrombotic complications, systemic symptoms, and curtailed survival due to infections, thrombo-hemorrhagic events, or progression to leukemic transformation. New drugs have been developed in the last decade for the treatment of PMF-associated symptoms; however, the only curative option is currently represented by allogeneic hematopoietic cell transplantation, which can only be offered to a small percentage of patients. Disease prognosis is based at diagnosis on the classical International Prognostic Scoring System (IPSS) and Dynamic-IPSS (during disease course), which comprehend clinical parameters; recently, new prognostic scoring systems, including genetic and molecular parameters, have been proposed as meaningful tools for a better patient stratification. Moreover, new biological markers predicting clinical evolution and patient survival have been associated with the disease. This review summarizes basic concepts of PMF pathogenesis, clinics, and therapy, focusing on classical prognostic scoring systems and new biological markers of the disease.

Citing Articles

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Systemic inflammatory indices for predicting prognosis of myelofibrosis.

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Gain-of-Function Variomics and Multi-omics Network Biology for Precision Medicine.

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References

James C, Ugo V, Le Couedic J, Staerk J, Delhommeau F, Lacout C . A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005; 434(7037):1144-8. DOI: 10.1038/nature03546. View

Barbui T, Carobbio A, Finazzi G, Guglielmelli P, Salmoiraghi S, Rosti V . Elevated C-reactive protein is associated with shortened leukemia-free survival in patients with myelofibrosis. Leukemia. 2013; 27(10):2084-6. DOI: 10.1038/leu.2013.207. View

Fucikova J, Spisek R, Kroemer G, Galluzzi L . Calreticulin and cancer. Cell Res. 2020; 31(1):5-16. PMC: 7853084. DOI: 10.1038/s41422-020-0383-9. View

Zetterberg E, Vannucchi A, Migliaccio A, Vainchenker W, Tulliez M, Dickie R . Pericyte coverage of abnormal blood vessels in myelofibrotic bone marrows. Haematologica. 2007; 92(5):597-604. DOI: 10.3324/haematol.11013. View

Rosti V, Villani L, Riboni R, Poletto V, Bonetti E, Tozzi L . Spleen endothelial cells from patients with myelofibrosis harbor the JAK2V617F mutation. Blood. 2012; 121(2):360-8. DOI: 10.1182/blood-2012-01-404889. View

Silver R, Vandris K . Recombinant interferon alpha (rIFN alpha-2b) may retard progression of early primary myelofibrosis. Leukemia. 2009; 23(7):1366-9. DOI: 10.1038/leu.2009.90. View

Rosti V, Massa M, Vannucchi A, Bergamaschi G, Campanelli R, Pecci A . The expression of CXCR4 is down-regulated on the CD34+ cells of patients with myelofibrosis with myeloid metaplasia. Blood Cells Mol Dis. 2007; 38(3):280-6. DOI: 10.1016/j.bcmd.2007.01.003. View

Pikman Y, Lee B, Mercher T, McDowell E, Ebert B, Gozo M . MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006; 3(7):e270. PMC: 1502153. DOI: 10.1371/journal.pmed.0030270. View

Baxter E, Scott L, Campbell P, East C, Fourouclas N, Swanton S . Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005; 365(9464):1054-61. DOI: 10.1016/S0140-6736(05)71142-9. View

10.

Koschmieder S, Mughal T, Hasselbalch H, Barosi G, Valent P, Kiladjian J . Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both. Leukemia. 2016; 30(5):1018-24. DOI: 10.1038/leu.2016.12. View

11.

Lin C, Kaushansky K, Zhan H . JAK2-mutant vascular niche contributes to JAK2 clonal expansion in myeloproliferative neoplasms. Blood Cells Mol Dis. 2016; 62:42-48. PMC: 5135612. DOI: 10.1016/j.bcmd.2016.09.004. View

12.

Walkley C, Olsen G, Dworkin S, Fabb S, Swann J, McArthur G . A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007; 129(6):1097-110. PMC: 1974882. DOI: 10.1016/j.cell.2007.05.014. View

13.

Geissler K, Gisslinger B, Jager E, Jager R, Schiefer A, Bogner E . Myelomonocytic Skewing In Vitro Discriminates Subgroups of Patients with Myelofibrosis with A Different Phenotype, A Different Mutational Profile and Different Prognosis. Cancers (Basel). 2020; 12(8). PMC: 7464756. DOI: 10.3390/cancers12082291. View

14.

Vannucchi A, Lasho T, Guglielmelli P, Biamonte F, Pardanani A, Pereira A . Mutations and prognosis in primary myelofibrosis. Leukemia. 2013; 27(9):1861-9. DOI: 10.1038/leu.2013.119. View

15.

Hasselbalch H . Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?. Leuk Res. 2012; 37(2):214-20. DOI: 10.1016/j.leukres.2012.10.020. View

16.

Sagaster V, Jager E, Weltermann A, Schwarzinger I, Gisslinger H, Lechner K . Circulating hematopoietic progenitor cells predict survival in patients with myelofibrosis with myeloid metaplasia. Haematologica. 2003; 88(11):1204-12. View

17.

Rumi E, Cazzola M . Diagnosis, risk stratification, and response evaluation in classical myeloproliferative neoplasms. Blood. 2016; 129(6):680-692. PMC: 5335805. DOI: 10.1182/blood-2016-10-695957. View

18.

Iurlo A, Cattaneo D, Bucelli C . Management of Myelofibrosis: from Diagnosis to New Target Therapies. Curr Treat Options Oncol. 2020; 21(6):46. DOI: 10.1007/s11864-020-00734-y. View

19.

Verstovsek S, Kantarjian H, Mesa R, Pardanani A, Cortes-Franco J, Thomas D . Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010; 363(12):1117-27. PMC: 5187954. DOI: 10.1056/NEJMoa1002028. View

20.

Bjorn M, Hasselbalch H . The Role of Reactive Oxygen Species in Myelofibrosis and Related Neoplasms. Mediators Inflamm. 2015; 2015:648090. PMC: 4619981. DOI: 10.1155/2015/648090. View