galectin-3

Pro- and Antifibrotic Factors in the Serum of Patients with Chronic Myeloproliferative Disorders

MYELOID TUMORS , , , ,

AA Silyutina, NM Matyukhina, EG Lisina, VI Khvan, SN Leleko, NT Siordiya, OV Sirotkina, PA Butylin

VA Almazov National Medical Research Center, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341

For correspondence: Pavel Andreevich Butylin, PhD, 2 Akkuratova str., Saint Petersburg, Russian Federation, 197341; e-mail: butylinp@gmail.com

For citation: Silyutina AA, Matyukhina NM, Lisina EG, et al. Pro- and Antifibrotic Factors in the Serum of Patients with Chronic Myeloproliferative Disorders. Clinical oncohematology. 2017;10(4):479–84 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-479-484

ABSTRACT

Background. The study of pro- and antifibrotic factors in the serum of patients with Ph-negative chronic myeloproliferative disorders (CMPDs) will allow to understand better the mechanisms of myelofibrosis development, as well as to identify new diagnostic markers.

Aim. To assess the correlation between the levels of classic (TGF-β, bFGF, MMP-2, -9, -13 and VEGF) and new proinflammatory serum factors (galectin-3), involved into development of myelofibrosis in different Ph-negative forms of CMPDs and genetic abnormalities.

Materials & Methods. The research included 55 CMPD patients (13 with polycythemia vera, 17 with essential thrombocythemia, 25 with primary myelofibrosis) and 8 healthy controls. Whole blood genomic DNA extraction was used to evaluate mutations JAK2V617F, CALR (deletions and insertions), MPLW515L, and MPLW515K. Antibody-immobilized ELISA was used to evaluate the levels of galectin-3, TGF-β, bFGF, VEGF, MMP-2, MMP-9 and MMP-13.

Results. The analysis showed the differences in serum MMP-9, VEGF, TGF-β and galectin-3 levels in patients with different CMPDs. A tendency towards the decrease of serum MMP-9 levels in patients with CALR mutations was shown.

Conclusion. The shown differences between patients with different CMPDs may serve as a basis for improving diagnostic protocols in challenging differential diagnosis of CMPDs.

Keywords: Ph-negative chronic myeloproliferative disorders, pro- and antifibrotic factors, JAK2V617F, CALR, MPLW515L, MPLW515K, MMP-2, MMP-9, MMP-13, galectin-3.

Received: April 26, 2017

Accepted: July 5, 2017

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REFERENCES

  1. Kiladjian J-J. The spectrum of JAK2-positive myeloproliferative neoplasms. Hematology. 2012;2012:561–6. doi: 10.1182/asheducation-2012.1.561.
  2. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391–405. doi: 10.1056/NEJMoa1312542.
  3. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379–90. doi: 10.1056/NEJMoa1311347.
  4. Li J, Kent DG, Chen E, Green AR. Mouse models of myeloproliferative neoplasms: JAK of all grades. Dis Model Mech. 2011;4(3):311–7. doi: 10.1242/dmm.006817.
  5. Parganas E, Wang D, Stravopodis D, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998;93(3):385–95. doi: 10.1016/s0092-8674(00)81167-8.
  6. Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008;22(2):437–8. doi: 10.1038/sj.leu.2404914.
  7. Hoffman R, Rondelli D. Biology and treatment of primary myelofibrosis. Hematology. 2007;2007(1):346–54. doi: 10.1182/asheducation-2007.1.346.
  8. Jacobson RJ, Salo A, Fialkow PJ. Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis. Blood. 1978;51(2):189–94.
  9. Reeder TL, Bailey RJ, Dewald GW, et al. Both B and T lymphocytes may be clonally involved in myelofibrosis with myeloid metaplasia. Blood. 2003;101(5):1981–3. doi: 10.1182/blood-2002-07-2341.
  10. Reilly JT. Idiopathic myelofibrosis: pathogenesis, natural history and management. Blood Rev. 1997;11(4):233–42. doi: 10.1016/S0268-960X(97)90022-9.
  11. Mesa RA, Hanson CA, Rajkumar SV, et al. Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia. Blood. 2000;96:3374–80.
  12. Tefferi A. The pathogenesis of chronic myeloproliferative diseases. Int J Hematol. 2001;73(2):170–6. doi: 10.1007/BF02981934.
  13. Chagraoui H, Komura E, Tulliez M, et al. Prominent role of TGF-beta 1 in thrombopoietin-induced myelofibrosis in mice. Blood. 2002;100(10):3495–503. doi: 10.1182/blood-2002-04-1133.
  14. Martyre MC, Le Bousse-Kerdiles C, Romquin N, et al. Elevated levels of basic growth factor in megakaryocytes and platelets from patients with idiopathic myelofibrosis. Br J Haematol. 1997;97(2):441–8. doi: 10.1046/j.1365-2141.1997.292671.x.
  15. Boiocchi L, Vener C, Savi F, et al. Increased expression of vascular endothelial growth factor receptor 1 correlates with VEGF and microvessel density in Philadelphia chromosome-negative myeloproliferative neoplasms. J Clin Pathol. 2011;64(3):226–31. doi: 10.1136/jcp.2010.083386.
  16. Giannandrea M, Parks WC. Diverse functions of matrix metalloproteinases during fibrosis. Dis Mod Mechan. 2014;7(2):193–203. doi: 10.1242/dmm.012062.
  17. Jensen MK, Holten-Andersen MN, Riisbro R, et al. Elevated plasma levels of TIMP-1 correlate with plasma suPAR/uPA in patients with chronic myeloproliferative disorders. Eur J Haematol. 2003;71(5):377–84. doi: 10.1034/j.1600-0609.2003.00096.x.
  18. Wang JC, Novetsky A, Chen C, Novetsky AD. Plasma matrix metalloproteinase and tissue inhibitor of metalloproteinase in patients with agnogenic myeloid metaplasia or idiopathic primary myelofibrosis. Br J Haematol. 2002;119(3):709–12. doi: 10.1046/j.1365-2141.2002.03874.x.
  19. Kim SY, Im K, Park SN, et al. CALR, JAK2, and MPL Mutation Profiles in Patients With Four Different Subtypes of Myeloproliferative Neoplasms: Primary Myelofibrosis, Essential Thrombocythemia, Polycythemia Vera, and Myeloproliferative Neoplasm, Unclassifiable. Am J Clin Pathol. 2015;143(5):635–44. doi: 10.1309/AJCPUAAC16LIWZMM.
  20. Gianelli U, Vener C, Raviele PR, et al. VEGF Expression Correlates With Microvessel Density in Philadelphia Chromosome–Negative Chronic Myeloproliferative Disorders. Am J Clin Pathol. 2007;128(6):966–73. doi: 10.1309/FP0N3LC8MBJUFFA6.
  21. Le Bousse-Kerdiles MC, Chevillard S, Charpentier A, et al. Differential expression of transforming growth factor-beta, basic fibroblast growth factor, and their receptors in CD34+ hematopoietic progenitor cells from patients with myelofibrosis and myeloid metaplasia. Blood. 1996;88:4534–46.
  22. Campanelli R, Rosti V, Villani L, et al. Evaluation of the bioactive and total transforming growth factor β1 levels in primary myelofibrosis. Cytokine. 2011;53(1):100–6. doi: 10.1016/j.cyto.2010.07.427.
  23. Силютина А.А., Гин И.И., Матюхина Н.М. и др. Модели миелофиброза (обзор литературы и собственные данные). Клиническая онкогематология. 2017;10(1):75–84. doi: 10.21320/2500-2139-2017-10-1-75-84.[Silyutina AA, Gin II, Matyukhina NM, et al. Myelofibrosis Models: Literature Review and Own Data. Clinical oncohematology. 2017;10(1):75–84. doi: 10.21320/2500-2139-2017-10-1-75-84. (In Russ)]
  24. Henderson NC, Mackinnon AC, Farnworth SL, et al. Galectin-3 regulates myofibroblast activation and hepatic fibrosis. Proc Nat Acad Sci USA. 2006;103(13):5060–5. doi: 10.1073/pnas.0511167103.
  25. Brand C, Oliveira F, Takiya C, et al. The involvement of the spleen during chronic phase of Schistosoma mansoni infection in galectin-3-/- mice. Histol Histopathol. 2012;27(8):1109–20. doi: 10.14670/HH-27.1109.
  26. Koopmans SM, Bot FJ, Schouten HC, et al. The involvement of Galectins in the modulation of the JAK/STAT pathway in myeloproliferative neoplasia. Am J Blood Res. 2012;2(2):119–27.