The Relationship of Hepcidin, Soluble Transferrin Receptor, Growth Differentiation Factor-15 And Anemia in Multipl Myeloma

Year 2023, , 369 - 376, 20.10.2023

Birgül Öneç , Durdu Mehmet Köş , Gulsah Altun , Mehmet Ali Sungur

https://doi.org/10.18521/ktd.1321364

Abstract

Objective: Multiple myeloma (MM) is a malignant hematological disease and anemia is observed in the majority of patients. Hepcidin, Growth differentiation factor-15 (GDF-15), soluble transferrin receptor (sTfR) have been investigated in many forms of anemia, especially in chronic diseases and cancers. However, there are few studies investigating their role in MM. We aimed to determine the relationship between hepcidin, sTfR and GDF-15 levels in MM patients and their clinical features such as anemia parameters, disease stage and overall survival.
Method: Hepcidin, sTfR and GDF-15 levels, as well as clinical and anemia-related parameters, were analyzed in newly diagnosed MM patients and healthy volunteers.
Result: Although MM patients had significantly lower Hb and Hct levels compared to the control group, none of the GDF-15, hepcidin and sTfR levels showed a significant difference between the groups. Among MM patients, we found that the anemic subgroup had significantly lower hepcidin levels than the non-anemic subgroup. GDF-15, hepcidin and sTfR levels showed weak or moderate positive correlation with each other, while GDF15 was positively correlated with creatinine and sTfR levels were correlated with many parameters such as LDH, CRP, ferritin, albumin, creatinine, Hb and ISS, all of which weak. None of the levels of GDF-15, hepcidin and sTfR had a significant effect on survival.
Conclusion: We suggested that these mediators may play a role in anemia of MM but there is not a clear relashionship as in chronic disease anemia, there may be different mechanisms according to the characteristics of the patient groups.

Keywords

Multipl myeloma, anemia, hepcidin, Growth differentiation factor-15, soluble transferrin receptor, sTfR, GDF-15

Supporting Institution

Scientific Research Project of Düzce University

Project Number

2015.04.03.336.

Thanks

This study is supported by Duzce University Scientific Research Projects Coordinator ship with project number of 2015.04.03.336 .

Multipl miyelom hastalarında hepsidin, solubl transferrin reseptörü ve büyüme farklılaşma faktörü-15’in anemiyle ilişkisi

Abstract

Amaç: Multipl myelom (MM) malign bir hematolojik hastalıktır ve hastaların çoğunluğunda anemi görülmektedir. Hepsidin, büyüme farklılaşma faktörü-15 (GDF-15), solubl transferrin reseptörü (sTfR) başta kronik hastalıklar ve kanserlerde olmak üzere birçok anemide çalışılmıştır ancak MM’daki anemide rollerini araştıran çalışmalar çok azdır. Multipl myelom hastalarında hepsidin, sTfR ve GDF-15 düzeylerini ve bu düzeylerin anemi parametreleri, hastalık evresi ve toplam sağkalım gibi klinik özelliklerle ilişkisini belirlemeyi amaçladık.
Metod: Yeni tanı almış MM hastalarında ve sağlıklı gönüllülerde hepsidin, sTfR ve GDF-15 düzeylerinin yanı sıra diğer klinik ve anemi ile ilişkili parametreler analiz edildi.
Bulgular: Miyelom hastaları kontrol grubuna göre belirgin düşük Hb ve Hct düzeylerine sahip olmalarına rağmen, GDF-15, hepsidin ve sTfR düzeylerinin hiçbiri gruplar arasında anlamlı bir farklılık göstermiyordu. MM hastaları içinde anemik alt grupta, anemik olmayan altgruba göre belirgin düşük hepsidin düzeyleri olduğunu saptadık. GDF-15, hepsidin ve sTfR düzeylerinin birbirleriyle zayıf ya orta düzeyde pozitif yönde korelasyon gösterirken, GDF15 kreatinin ile pozitif yönde köreleydi ve sTfR düzeyleri ise LDH, CRP, ferritin, albümin, kreatinin, Hb ve ISS evresi gibi birçok parametre ile ancak zayıf düzeyde korelasyon gösteriyordu. GDF-15, hepsidin ve sTfR düzeylerinin hiçbiri sağkalım üzerine anlamlı etkiye sahip değildi.
Sonuç: Bu mediyatörlerinin MM anemisinde bir rolü olabileceğini ancak kronik hastalık anemisindeki gibi net bir ilişki olmadığını, hasta gruplarının özelliklerine göre değişken mekanizmalar olabileceğini düşündürmüştür.

Keywords

Multipl miyelom, anemi, hepsidin, büyüme farklılaşma faktörü-15, soluble transferrin reseptörü, sTfR

Project Number

2015.04.03.336.

References

• 1. Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, et al. In anemia of multiple myeloma, hepcidin is induced by increased bone morphogenetic protein 2. Blood. 2010;116(18):3635-44.
• 2. Konig C, Kleber M, Ihorst G, Gropp A, Reinhardt H, Koch B, et al. Prevalence of iron overload vs iron deficiency in multiple myeloma: resembling or different from MDS--and stem cell transplant (SCT)--patients? Clinical lymphoma, myeloma & leukemia. 2013;13(6):671-80
• 3. Zhao N, Zhang AS, Enns CA. Iron regulation by hepcidin. The Journal of clinical investigation. 2013;123(6):2337-43.
• 4. Evstatiev R, Gasche C. Iron sensing and signaling. Gout. 2012;61(6):933-52.
• 5. Jiang F, Yu WJ, Wang XH, Tang YT, Guo L, Jiao XY. Regulation of hepcidin through GDF-15 in cancer-related anemia. Clinica chimica acta; international journal of clinical chemistry. 2014; 428:14 -9.
• 6. Johnen H, Lin S, Kuffner T, Brown DA, Tsai VW, Bauskin AR, et al. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. nature medicine. 2007;13(11):1333-40.
• 7. Koopmann J, Buckhaults P, Brown DA, Zahurak ML, Sato N, Fukushima N, et al. Serum macrophage inhibitory cytokine 1 as a marker of pancreatic and other periampullary cancers. Clinical cancer research : an official journal of the American Association for Cancer Research. 2004;10(7):2386-92.
• 8. Karan D, Holzbeierlein J, Thrasher JB. Macrophage inhibitory cytokine-1: possible bridge molecule of inflammation and prostate cancer. Cancer research. 2009;69(1):2-5.
• 9. Bauskin AR, Brown DA, Kuffner T, Johnen H, Luo XW, Hunter M, et al. Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer. Cancer research. 2006;66(10):4983-6.
• 10. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, et al. High levels of GDF-15in thalassemia suppress expression of the iron regulatory protein hepcidin. nature medicine. 2007;13(9):1096-101.
• 11. Tamary H, Shalev H, Perez-Avraham G, Zoldan M, Levi I, Swinkels DW, et al. Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I. Blood. 2008;112(13):5241-4.
• 12. Finkenstedt A, Bianchi P, Theurl I, Vogel W, Witcher DR, Wroblewski VJ, et al. Regulation of iron metabolism through GDF-15and hepcidin in pyruvate kinase deficiency. British journal of haematology. 2009;144(5):789-93.
• 13. Fertrin KY, Lanaro C, Franco-Penteado CF, de Albuquerque DM, de Mello MR, Pallis FR, et al. Erythropoiesis-driven regulation of hepcidin in human red cell disorders is better reflected through concentrations of soluble transferrin receptor rather than growth differentiation factor 15. American journal of hematology. 2014;89(4):385-90.
• 14. Tarkun P, Birtas Atesoglu E, Mehtap O, Musul MM, Hacihanefioglu A. Serum growth differentiation factor 15 levels in newly diagnosed multiple myeloma patients. Acta haematologica. 2014;131(3):173-8.
• 15. Sharma S, Nemeth E, Chen YH, Goodnough J, Huston A, Roodman GD, et al. Involvement of hepcidin in the anemia of multiple myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008;14(11):3262-7.
• 16. Cucuianu A, Patiu M, Rusu A. Hepcidin and multiple myeloma related anemia. medical hypotheses. 2006;66(2):352-4.
• 17. Broome HE. Plasma cell neoplasms: general considerations. In: Kenneth Kaushansky MAL, E. Beutler, Thomas Kipps, Uri Seligsohn, Josef T. Prchal , editor. Williams Hematology. Eighth Edition ed: McGraw-Hill Professional; 2010.p. 1627-34.
• 18. Munshi NC, Jagannath S. Plasma cell neoplasms. In: Ronald Hoffman EJB, Jr. , Leslie Silberstein, Helen Heslop, Jeffrey Weitz, John Anastasi, editor. Hematology, Basic Principles and Practice. Sixth Edition ed: Saunders; 2013. p. 1303-37.
• 19. Morgan GJ, Davies FE, Linet M. Myeloma aetiology and epidemiology. Biomedicine & pharmacotherapy = Biomedicine & pharmacotherapy. 2002;56(5):223-34.
• 20. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005;55(2):74-108.
• 21. Vlasveld LT. Low cobalamin (vitamin B12) levels in multiple myeloma: a retrospective study. Neth J Med. 2003;61(8):249-52.
• 22. V. Pant, A. Tumbapo, and B. Kumar Yadav. Vitamin B12 immunoassay interference in a patient with multiple myeloma – troubleshooting in a two step reagent kit based on enhanced chemiluminescence testing. EJIFCC. 2018;29(2): 152–5.
• 23. Song MK1, Chung JS, Seol YM, Shin HJ, Choi YJ, Cho GJ. Elevation of serum ferritin is associated with the outcome of patients with newly diagnosed multiple myeloma. Korean J Intern Med. 2009;24(4):368-73.
• 24. Victor M, Evgeniy H, Gergana T, Julia P, Vasil V, Borislav M, Ivo B, Zlatina G, Kamen T. Serum Hepcidin Levels in Multiple Myeloma. Clin Lab. 2017;63(7):1273-7.
• 25. Haraguchi K, Uto H, Ohnou N, Tokunaga M, Tokunaga M, Utsunomiya A, Hanada S, Tsubouchi H. Serum prohepcidin levels are potential prognostic markers in patients with multiple myeloma. ExpTherMed. 2012;4(4):581-8.