Variant Signaling: Genetic, Hematologic and Immune Implication in Chronic Myeloproliferative Neoplasms

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2022 Feb 25

PMID 35204792

Authors

Dania G Torres

Jhemerson Paes

Allyson G da Costa

Adriana Malheiro

George V Silva

Lucivana P de Souza Mourao

Andrea M Tarrago

Affiliations

Soon will be listed here.

Abstract

The V617F variant constitutes a genetic alteration of higher frequency in BCR/ABL1 negative chronic myeloproliferative neoplasms, which is caused by a substitution of a G ˃ T at position 1849 and results in the substitution of valine with phenylalanine at codon 617 of the polypeptide chain. Clinical, morphological and molecular genetic features define the diagnosis criteria of polycythemia vera, essential thrombocythemia and primary myelofibrosis. Currently, V617F is associated with clonal hematopoiesis, genomic instability, dysregulations in hemostasis and immune response. V617F clones induce an inflammatory immune response and lead to a process of immunothrombosis. Recent research has shown great interest in trying to understand the mechanisms associated with V617F signaling and activation of cellular and molecular responses that progressively contribute to the development of inflammatory and vascular conditions in association with chronic myeloproliferative neoplasms. Thus, the aim of this review is to describe the main genetic, hematological and immunological findings that are linked to JAK2 variant signaling in chronic myeloproliferative neoplasms.

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References

Helbig G, Wichary R, Torba K, Kyrcz-Krzemien S . Resolution of thrombocytopenia, but not polycythemia after ruxolitinib for polycythemia vera with detectable mutation in the exon 12 of the JAK2 gene. Med Oncol. 2017; 34(3):31. PMC: 5263189. DOI: 10.1007/s12032-017-0891-8. View

Helbig G . Classical Philadelphia-negative myeloproliferative neoplasms: focus on mutations and JAK2 inhibitors. Med Oncol. 2018; 35(9):119. PMC: 6096973. DOI: 10.1007/s12032-018-1187-3. View

Ginzburg Y, Feola M, Zimran E, Varkonyi J, Ganz T, Hoffman R . Dysregulated iron metabolism in polycythemia vera: etiology and consequences. Leukemia. 2018; 32(10):2105-2116. PMC: 6170398. DOI: 10.1038/s41375-018-0207-9. View

Oh S . Neutralize the neutrophils! Neutrophil β1/β2 integrin activation contributes to JAK2-V617F-driven thrombosis. J Clin Invest. 2018; 128(10):4248-4250. PMC: 6159984. DOI: 10.1172/JCI123388. View

Means R . JAK2 V617F and the evolving paradigm of polycythemia vera. Korean J Hematol. 2010; 45(2):90-4. PMC: 2983020. DOI: 10.5045/kjh.2010.45.2.90. View

McKenna E, Ui Mhaonaigh A, Wubben R, Dwivedi A, Hurley T, Kelly L . Neutrophils: Need for Standardized Nomenclature. Front Immunol. 2021; 12:602963. PMC: 8081893. DOI: 10.3389/fimmu.2021.602963. View

Gonzalez-Rodriguez A, Villa-Alvarez M, Sordo-Bahamonde C, Lorenzo-Herrero S, Gonzalez S . NK Cells in the Treatment of Hematological Malignancies. J Clin Med. 2019; 8(10). PMC: 6832953. DOI: 10.3390/jcm8101557. 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

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

10.

Habbel J, Arnold L, Chen Y, Mollmann M, Bruderek K, Brandau S . Inflammation-driven activation of JAK/STAT signaling reversibly accelerates acute myeloid leukemia in vitro. Blood Adv. 2020; 4(13):3000-3010. PMC: 7362361. DOI: 10.1182/bloodadvances.2019001292. View

11.

Tefferi A . Myeloproliferative neoplasms: A decade of discoveries and treatment advances. Am J Hematol. 2015; 91(1):50-8. DOI: 10.1002/ajh.24221. View

12.

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

13.

Gaman M, Cozma M, Dobrica E, Cretoiu S, Gaman A, Diaconu C . Liquid Biopsy and Potential Liquid Biopsy-Based Biomarkers in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review. Life (Basel). 2021; 11(7). PMC: 8304270. DOI: 10.3390/life11070677. View

14.

Freitas R, da Costa Maranduba C . Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview. Rev Bras Hematol Hemoter. 2015; 37(5):348-53. PMC: 4685044. DOI: 10.1016/j.bjhh.2014.10.001. View

15.

Hinds D, Barnholt K, Mesa R, Kiefer A, Do C, Eriksson N . Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms. Blood. 2016; 128(8):1121-8. PMC: 5085254. DOI: 10.1182/blood-2015-06-652941. View

16.

Gaertner F, Massberg S . Blood coagulation in immunothrombosis-At the frontline of intravascular immunity. Semin Immunol. 2016; 28(6):561-569. DOI: 10.1016/j.smim.2016.10.010. View

17.

Barbui T, Thiele J, Gisslinger H, Kvasnicka H, Vannucchi A, Guglielmelli P . The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018; 8(2):15. PMC: 5807384. DOI: 10.1038/s41408-018-0054-y. View

18.

Tefferi A, Barbui T . Polycythemia vera and essential thrombocythemia: 2019 update on diagnosis, risk-stratification and management. Am J Hematol. 2018; 94(1):133-143. DOI: 10.1002/ajh.25303. View

19.

Kaifie A, Kirschner M, Wolf D, Maintz C, Hanel M, Gattermann N . Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry. J Hematol Oncol. 2016; 9:18. PMC: 4779229. DOI: 10.1186/s13045-016-0242-9. View

20.

Yonal-Hindilerden I, Daglar-Aday A, Akadam-Teker B, Yilmaz C, Nalcaci M, Yavuz A . Prognostic significance of ASXL1, JAK2V617F mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms. J Blood Med. 2015; 6:157-75. PMC: 4459634. DOI: 10.2147/JBM.S78826. View