Anemia of Chronic Diseases

NV Kurkina, EI Gorshenina, LV Chegodaeva, AV Polagimova

NP Ogarev National Research Mordovia State University, 68 Bolshevistskaya str., Saransk, Russian Federation, 430005

For correspondence: Nadezhda Viktorovna Kurkina, MD, PhD, 26А Ul’yanova str., Saransk, Russian Federation, 430032; Tel.: +7(927)172-48-63; e-mail:

For citation: Kurkina NV, Gorshenina EI, Chegodaeva LV, Polagimova AV. Anemia of Chronic Diseases. Clinical oncohematology. 2021;14(3):347–54. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-347-354


Anemia of chronic diseases (ACD) refers to a group of anemias arising in various inflammatory infections, autoimmune or tumor diseases due to acute or chronic immune activation. ACD ranks second in incidence after iron deficiency anemia (IDA). Within the variety of pathogenetic mechanisms one of the primary ones is hepcidin synthesis in hepatocytes, which blocks iron absorption in the intestine and contributes to its deposition in cells of the monocyte-macrophage system. Besides, excessive cytokines in such diseases and pathologies lead to lower erythropoietin production which does not correspond to the severity grade of anemia. This results in impaired erythropoiesis in the bone marrow. The differential diagnosis should also specify iron deficiency type (the absolute one in IDA and the functional one in ACD). The effective treatment of the main disease and anemia correction speed up the improvement of patient’s status, rehabilitation, and quality of life.

Keywords: anemia, chronic diseases, immune system, hepcidin, cytokines, erythropoietin, ferritin, serum iron.

Received: January 17, 2021

Accepted: April 30, 2021

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Статистика Plumx английский


  1. Андреичев Н.А., Балеева Л.В. Анемия хронических заболеваний. Российский медицинский журнал. 2014;20(2):50–5.
    [Andreichev NA, Baleeva LV. Anemia of chronic diseases. Rossiiskii meditsinskii zhurnal. 2014;20(2):50–5. (In Russ)]
  2. Волкова С.А., Боровков Н.Н. Основы клинической гематологии: учебное пособие. Н. Новгород: НижГМА, 2013. 400 с.
    [Volkova SA, Borovkov NN. Osnovy klinicheskoi gematologii: uchebnoe posobie. (Fundamentals of clinical hematology: learning guide.) Nizhny Novgorod: NizhGMA Publ.; 2013. 400 p. (In Russ)]
  3. John M, Hoernig S, Doehner W, et al. Anemia and inflammation in COPD. Chest. 2005;127(3):825–9. doi: 10.1378/chest.127.3.825.
  4. Будневский А.В., Есауленко И.Е., Овсянников Е.С., Жусина Ю.Г. Анемия при хронической обструктивной болезни легких. Терапевтический архив. 2016;88(3):96–9. doi: 10.17116/terarkh201688396-99.
    [Budnevsky AV, Esaulenko IE, Ovsyannikov ES, Zhusina YuG. Anemia in chronic obstructive pulmonary disease. Terapevticheskii arkhiv. 2016;88(3):96–9. doi: 10.17116/terarkh201688396-99. (In Russ)]
  5. Жусина Ю.Г., Будневский А.В., Феськова А.А., Овсянников Е.С. О взаимосвязи хронической обструктивной болезни легких и анемии. Пульмонология. 2018;28(6):730–5. doi: 10.18093/0869-0189-2018-28-6-730-735.
    [Zhusina YuG, Budnevskiy AV, Fes’kova AA, Ovsyannikov ES. About relationship between chronic obstructive pulmonary disease and anemia. Pulmonologiya. 2018;28(6):730–5. doi: 10.18093/0869-0189-2018-28-6-730-735. (In Russ)]
  6. Tsantes AE, Tassiopoulos ST, Papadhimitriou SI, et al. Theophylline treatment may adversely affect the anoxia-induced erythropoietic response without suppressing erythropoietin production. Eur J Clin Pharmacol. 2003;59(5–6):379–83. doi: 10.1007/s00228-003-0640-0.
  7. Marathias KP, Agroyannis B, Mavromoustakos T, et al. Hematocrit-lowering effect following inactivation of renin-angiotensin system with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Curr Top Med Chem. 2004;4(4):483–6. doi: 10.2174/1568026043451311.
  8. Рукавицын О.А. Гематология. Национальное руководство. М.: ГЭОТАР-Медиа, 2017. 784 с.
    [Rukavitsyn OA. Natsional’noe rukovodstvo. (Hematology. National Guidelines.) Moscow: GEOTAR-Media Publ.; 2017. 784 p. (In Russ)]
  9. Groenveld HF, Januzzi JL, Damman K, et al. Anemia and mortality in heart failure patients a systematic review and meta-analysis. J Am Coll Cardiol. 2008;52(10):818–27. doi: 10.1016/j.jacc.2008.04.061.
  10. Снеговой А.В., Aapro M., Гладков О.А. и др. Практические рекомендации по лечению анемии у онкологических больных. Злокачественные опухоли. 2016;4:368–77.
    [Snegovoi AV, Aapro M, Gladkov OA, et al. Practical guidelines for anemia treatment in oncological patients. Zlokachestvennye opukholi. 2016;4:368–77. (In Russ)]
  11. Voulgari PV, Kolios G, Papadopoulos GK, et al. Role of cytokines in the pathogenesis of anemia of chronic disease in rheumatoid arthritis. Clin Immunol. 1999;92(2):153–60. doi: 10.1006/clim.1999.4736.
  12. Stauffer ME, Fan T. Prevalence of Anemia in Chronic Kidney Disease in the United States. PLoS One. 2014;9(1):e84943. doi: 10.1371/journal.pone.0084943.
  13. McClellan W, Aronoff SL, Bolton WK, et al. The prevalence of anemia in patients with chronic kidney disease. Curr Med Ress Opion. 2004;20(9):1501–10. doi: 10.1185/030079904X2763.
  14. Stenvinkel P. The role of inflammation in the anaemia of end-stage renal disease. Nephrol Dial Transplant. 2001;16(Suppl 7):36–40. doi: 10.1093/ndt/16.suppl_7.36.
  15. Thorp ML, Johnson ES. Effect of anemia on mortality, cardiovascular hospitalizations and end stage renal disease among patients with chronic kidney disease. Nephrology. 2009;14(2):240–6. doi: 10.1111/j.1440-1797.2008.01065.x.
  16. Andrews M, Arredondo M. Ferritin levels and hepcidin mRNA expression in peripheral mononuclear cells from anemic type 2 diabetic patients. Biol Trace Elem Res. 2012;149(1):1–4. doi: 10.1007/s12011-012-9389-6.
  17. Zoppini G, Targher G, Chonchol M, et al. Anaemia, independent of chronic kidney disease, predicts all cause and cardiovascular mortality in type 2 diabetic patients. Atherosclerosis. 2010;210(2):575–80. doi: 10.1016/j.atherosclerosis.2009.12.008.
  18. Ito H, Takeuchi Y, Ishida H, et al. Mild anemia is frequent and associated with micro- and macroangiopathies in patients with type 2 diabetes mellitus. J Diab Invest. 2010;1(6):273–8. doi: 10.1111/j.2040-1124.2010.00060.x.
  19. Roy CN, Mak HH, Akpan I, et al. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood. 2007;109(9):4038–44. doi: 10.1182/blood-2006-10-051755.
  20. Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol. 2009;46(4):387–393. doi: 10.1053/j.seminhematol.2009.06.001.
  21. Морщакова Е.Ф., Павлов А.Д., Румянцев А.Г. Эритропоэз, эритропоэтин, железо. М.: ГЭОТАР-Медиа, 2013. 178 с.
    [Morshchakova EF, Pavlov AD, Rumyantsev AG. Eritropoez, eritropoetin, zhelezo. (Erythropoiesis, erythropoietin, iron.) Moscow: GEOTAR-Media Publ.; 2013. 178 p. (In Russ)]
  22. Рукавицын О.А. Анемия хронических заболеваний: отдельные аспекты патогенеза и пути коррекции. Онкогематология. 2016;11(1):37–46. doi: 10.17650/1818-8346-2016-11-1-37-46.
    [Rukavitsyn OA. Anemia of chronic diseases: the important aspects of pathogenesis and treatment. Oncohematology. 2016;11(1):37–46. doi: 10.17650/1818-8346-2016-11-1-37-46. (In Russ)]
  23. Румянцев А.Г., Масчан А.А. Федеральные клинические рекомендации по диагностике и лечению анемии хронических заболеваний (электронный документ). Доступно по: Ссылка активна на 13.04.2021.
    [Rumyantsev AG, Maschan AA. Federal clinical guidelines for diagnosis and treatment of anemia of chronic diseases. [Internet] Available from: (accessed 13.04.2021) (In Russ)]
  24. Nemeth E, Ganz T. Anemia of Inflammation. Hematol Oncol Clin North Am. 2014;28(4):671–81. doi: 10.1016/j.hoc.2014.04.005.
  25. Weiss Pathogenesis and treatment of anemia of chronic disease. Blood Rev. 2002;16(2):87–96. doi: 10.1054/blre.2002.0193.
  26. Сморкалова Е.В. Иммуногематологические особенности железодефицитной анемии и анемии хронических заболеваний: Автореф. дис.… канд. мед. наук. Уфа, 2012. 22 с.
    [Smorkalova EV. Immunogematologicheskie osobennosti zhelezodefitsitnoi anemii i anemii khronicheskikh zabolevanii. (Immunohematological characteristics of iron deficiency anemia and anemia of chronic diseases.) [dissertation] Ufa; 2012. 22 p. (In Russ)]
  27. Kato Y, Takagi C, Tanaka J, et al. Effect of daily subcutaneous administration of recombinant erythropoietin on chronic anemia in rheumatoid arthritis. Intern Med. 1994;33(4):193–7. doi: 10.2169/internalmedicine.33.193.
  28. Peeters HR, Jongen-Lavrencic M, Bakker CH, et al. Recombinant human erythropoietin improves health-related quality of life in patients with rheumatoid arthritis and anaemia of chronic disease; utility measures correlate strongly with disease activity measures. Rheumatol Int. 1999;18(5–6):201–6. doi: 10.1007/s002960050085.
  29. Arndt U, Kaltwasser JP, Gottschalk R, et al. Correction of iron-deficient erythropoiesis in the treatment of anemia of chronic disease with recombinant human erythropoietin. Ann Hematol. 2005;84(3):159–66. doi: 10.1007/s00277-004-0950-z.
  30. Schipperus M, Rijnbeek B, Reddy M, et al. CNTO328 (Anti-IL-6 mAb) Treatment Is Associated with An Increase in Hemoglobin (Hb) and Decrease in Hepcidin Levels in Renal Cell Carcinoma (RCC). Blood. 2009;114(22):4045. doi: 10.1182/blood.v114.22.4045.4045.
  31. Hohlbaum A, Gille H, Christian J, et al. Iron mobilization and pharmacodynamic marker measurements in non-human primates following administration of PRS-080, a novel and highly specific antihepcidin therapeutic. Am J Hematol. 2013;88(5):E41.
  32. Schwoebel F, van Eijk LT, Zboralski D, et al. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomolgus monkeys. Blood. 2013;121(12):2311–5. doi: 10.1182/blood-2012-09-456756.
  33. Poli M, Girelli D, Campostrini N, et al. Heparin: a potent inhibitor of hepcidin expression in vitro and in vivo. Blood. 2011;117(3):997–1004. doi: 10.1182/blood-2010-06-289082.
  34. Crosby JR, Gaarde WA, Egerston J, et al. Targeting hepcidin with antisense oligonucleotides improves anemia endpoints in mice. Blood. 2006;108(11, Pt 1):269. doi: 10.1182/blood.v108.11.269.269.
  35. Akinc A, Chan-Daniels A, Sehgal A, et al. Targeting the hepcidin pathway with RNAi therapeutics for the treatment of anemia. Blood. 2011;118(21):688. doi: 10.1182/blood.v118.21.688.688.
  36. Гармиш Е.А. Анемия хронического воспаления при ревматоидном артрите: патогенез и выбор терапии. Украинский ревматологический журнал. 2016;1(63):39–41.
    [Garmish EА. Anemia of chronic inflammation of rheumatoid arthritis: pathogenesis and choice of treatment. Ukrainskii revmatologicheskii zhurnal. 2016;1(63):39–41. (In Russ)]

Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation

SP Svitina, ZhYu Sidorova, II Kostroma, AA Zhernyakova, AV Chechetkin, ZhV Chubukina, SV Gritsaev, SI Kapustin, SS Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Pavlovna Svitina, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; e-mail:

For citation: Svitina SP, Sidorova ZhYu, Kostroma II, et al. Polymorphism of Interleukins and Tumor Necrosis Factor α Genes in Multiple Myeloma Patients with Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2021;14(3):340–6. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-340-346


Aim. To assess polymorphism value of interleukins (IL6, IL1B, IL10) and tumor necrosis factor α (TNF) genes in multiple myeloma (MM) patients who received autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The study enrolled 37 MM patients (15 men and 22 women) aged 38–66 years (mean age 54.5 ± 6.4 years), who received auto-HSCT. After transplantation, partial (PR), very good partial (VGPR), and complete (CR) responses were reported in 11, 7, and 19 patients, respectively. In 23 (62.2 %) patients CD34+ cell collection on the day of the first leukocytapheresis session exceeded the suboptimal level of 2.5 × 106/kg. The control group included 236 healthy subjects. Genotyping by PCR with subsequent analysis of restriction fragment length polymorphism of amplified products was performed. To identify between-group differences in genotype distribution, Fisher’s exact test with measurements of odds ratio (OR) and рvalue was used.

Results. The study group of patients was distinguished from the control group by more than twofold increased proportion of homozygous IL1B –31C (OR 2.7; = 0.029). The proportion of heterozygous –174G/C allelic variant of IL6 gene in the subgroup of patients with CR after auto-HSCT was considerably higher than in patients with VGPR and PR (OR 5.6; = 0.022). In the subgroup of patients with CD34+ cell collection > 2.5 × 106/kg the proportion of those with IL10 –592C/C genotype was twice as high as in patients with lower CD34+ cell collection (OR 3.9; = 0.091).

Conclusion. The present study confirms the relationship of –31C/Т polymorphism in IL1B gene in homozygous state with higher MM risk. It proved the association of –174G/C polymorphism in IL6 gene and –592C/A polymorphism in IL10 gene with the chosen criteria for auto-HSCT efficacy. To precisely clarify the value of variants in the above genes for predicting chemotherapy effect in MM, further studies involving more patients are required.

Keywords: multiple myeloma, genes polymorphism, immune response, cytokines, autologous hematopoietic stem cell transplantation.

Received: March 4, 2021

Accepted: June 10, 2021

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Статистика Plumx английский


  1. Бессмельцев С.С. Множественная миелома (патогенез, клиника, диагностика, дифференциальный диагноз). Часть Клиническая онкогематология. 2013;6(3):237–57.
    [Bessmeltsev SS. Multiple myeloma (pathogenesis, clinical features, diagnosis, differential diagnosis). Part I. Klinicheskaya onkogematologiya. 2013;6(3):237–57. (In Russ)]
  2. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома: руководство для врачей. М.: СИМК, 2016. 512 с.
    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma: rukovodstvo dlya vrachei. (Multiple myeloma: manual for physicians.) Moscow: SIMK Publ.; 2016. 512 p. (In Russ)]
  3. Грицаев С.В., Кузяева А.А., Бессмельцев С.С. Отдельные аспекты аутологичной трансплантации гемопоэтических стволовых клеток при множественной миеломе. Клиническая онкогематология. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12.
    [Gritsaev SV, Kuzyaeva AA, Bessmel’tsev SS. Certain Aspects of Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma. Clinical oncohematology. 2017;10(1):7–12. doi: 10.21320/2500-2139-2017-10-1-7-12. (In Russ)]
  4. Бессмельцев С.С. Множественная миелома (лечение первичных больных): обзор литературы и собственные данные. Часть Клиническая онкогематология. 2013;6(4):379–414.
    [Bessmeltsev SS. Multiple myeloma (management of newly diagnosed patients): literature review and our on data. Part II. Klinicheskaya onkogematologiya. 2013;6(4):379–414. (In Russ)]
  5. Бессмельцев С.С., Абдулкадыров К.М. Множественная миелома. Современный взгляд на проблему. Алматы: Коста, 2007. 480 c.
    [Bessmeltsev SS, Abdulkadyrov KM. Mnozhestvennaya mieloma. Sovremennyi vzglyad na problemu. (Multiple myeloma. Current view on the problem.) Almaty: Kosta Publ.; 2007. 480 p. (In Russ)]
  6. Назарова Е.Л., Минаева Н.В., Хоробрых М.Н. и др. Прогностическое значение генетических маркеров в оценке эффективности индукционной терапии, включающей аутологичную трансплантацию гемопоэтических стволовых клеток, у больных множественной миеломой. Клиническая онкогематология. 2018;11(1):54–69. doi: 10.21320/2500-2139-2018-11-1-54-69.
    [Nazarova EL, Minaeva NV, Khorobrykh MN, et al. Prognostic Value of Genetic Markers for Efficacy Estimation of Induction Treatment Including Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients. Clinical oncohematology. 2018;11(1):54–69. doi: 10.21320/2500-2139-2018-11-1-54-69. (In Russ)]
  7. Vangsted AJ, Klausen TW, Ruminski W, et al. The polymorphism IL-1β T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT. Bone Marrow Transplant. 2009;43(7):539–45. doi: 10.1038/bmt.2008.351.
  8. Kasamatsu T, Saitoh T, Ino R, et al. Polymorphism of IL-10 receptor β affects the prognosis of multiple myeloma patients treated with thalidomide and/or bortezomib. Hematol Oncol. 2017;35(4):711–18. doi: 10.1002/hon.2322.
  9. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res. 1988;16(3):1215–8. doi: 10.1093/nar/16.3.1215.
  10. Mullis KB, Faloona FA. Specific synthesis of DNA via a polymerase-catalysed chain reaction. Methods Enzymol. 1987;155:335–50. doi: 10.1016/0076-6879(87)55023-6.
  11. Zheng C, Huang DR, Bergenbrant S, et al. Interleukin 6, tumor necrosis factor alpha, interleukin 1 beta and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol. 2000;109(1):39– doi: 10.1046/j.1365-2141.2000.01963.x.
  12. Wang X, Jiang F, Liang Y, et al. Interleukin-1β -31C/T and -511T/C Polymorphisms Were Associated with Preeclampsia in Chinese Han Population. PLoS One. 2014;9(9):1– doi: 10.18632/oncotarget.23472.
  13. Alexander DD, Mink PJ, Adami HO, et al. Multiple myeloma: a review of the epidemiologic literature. Int J Cancer. 2007;120(S12):40–61. doi: 10.1002/ijc.22718.
  14. Павлова А.А., Павлова И.Е., Бубнова Л.Н. и др. Взаимосвязь однонуклеотидного полиморфизма генов цитокинов и клинико-лабораторных показателей у больных множественной миеломой. Медицинская иммунология. 2019;21(4):703–14. doi: 10.15789/1563-0625-2019-4-703-714.
    [Pavlova AA, Pavlova IE, Bubnova LN, et al. Relationship between single nucleotide polymorphisms in cytokine genes and clinical laboratory parameters in patients with multiple myeloma. Meditsinskaya Immunologiya. 2019;21(4):703–14. doi: 10.15789/1563-0625-2019-4-703-714. (In Russ)]
  15. Ghobrial IM. Myeloma as a model for the process of metastasis: implications for therapy. Blood. 2012;120(1):20–30. doi: 10.1182/blood-2012-01-379024.
  16. Насонов Е.Л. Роль интерлейкина 1 в развитии заболеваний человека. Научно-практическая ревматология. 2018;56:19–27. doi: 10.14412/1995-4484-2018-19-27.
    [Nasonov EL. The role of interleukin 1 in the development of human diseases. Nauchno-Prakticheskaya Revmatologiya. 2018;56:19–27. doi: 10.14412/1995-4484-2018-19-27. (In Russ)]
  17. Costes V, Portier M, Lu ZY, et al. Interleukin-1 in multiple myeloma: producer cells and their role in the control of IL-6 production. Br J Haematol. 1998;103(4):1152–60. doi: 10.1046/j.1365-2141.1998.01101.x.
  18. Lacy MQ, Donovan KA, Heimbach JK, et al. Comparison of interleukin-1 beta expression by in situ hybridization in monoclonal gammopathy of undetermined significance and multiple myeloma. Blood. 1999;93(1):300–5. doi: 10.1182/blood.V93.1.300.
  19. Xiong Y, Donovan KA, Kline MP, et al. Identification of two groups of smoldering multiple myeloma patients who are either high or low producers of interleukin-1. J Interferon Cytokine Res. 2006;26(2):83–95. doi: 0.1089/jir.2006.26.83.
  20. Honemann D, Chatterjee M, Savino R, et al. The IL-6 receptor antagonist SANT-7 overcomes bone marrow stromal cell-mediated drug resistance of multiple myeloma cells. Int J Cancer. 2001;93(5):674–80. doi: 10.1002/ijc.1388.
  21. Lauta VM. A review of the cytokine network in multiple myeloma: diagnostic, prognostic, and therapeutic implications. Cancer. 2003;97(10):2440–52. doi: 10.1002/cncr.11072.
  22. Chakraborty B, Vishnoi G, Gowda SH, Goswami B. Interleukin-6 gene-174 G/C promoter polymorphism and its association with clinical profile of patients with multiple myeloma. Asia Pac J Clin Oncol. 2014;13(5):402–7. doi: 10.1111/ajco.12290.
  23. Terry CF, Loukaci V, Green FR. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000;275(24):18138–44. doi: 10.1074/jbc.M000379200.
  24. Ray A, Sassone-Corsi P, Sehgal PB. A multiple cytokine- and second messenger-responsive element in the enhancer of the human interleukin-6 gene: similarities with c-fos gene regulation. Mol Cell Biol. 1989;9(12):5537–47. doi: 10.1128/mcb.9.12.5537.
  25. Duch CR, Figueiredo MS, Ribas C, et al. Analysis of polymorphism at site -174 G/C of interleukin-6 promoter region in multiple myeloma. Braz J Med Biol Res. 2007;40(2):265–7. doi: 10.1590/s0100-879х2007000200014.
  26. Mazur G, Bogunia-Kubik K, Wrobel T, et al. IL-6 and IL-10 promoter gene polymorphisms do not associate with the susceptibility for multiple myeloma. Immunol Lett. 2005;96(2):241–6. doi: 10.1016/j.imlet.2004.08.015.
  27. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucl Acids Res. 1988;16(3):1215–8. doi: 10.1093/nar/16.3.1215.
  28. Banu C, Moise A, Arion CV, et al. Cytokine Gene Polymorphisms support diagnostic monitoring of Romanian multiple myeloma patients. J Med Life. 2011;4(3):264–8.
  29. Rousset F, Garcia E, Defrance T, et al. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA. 1992;89(5):1890–3. doi: 10.1073/pnas.89.5.1890.
  30. Taga K, Tosato G. IL-10 inhibits human T cell proliferation and IL-2 production. J Immunol. 1992;148(4):1143–8.
  31. Mosser DM, Zhang X. Interleukin-10: new perspectives on an old cytokine. Immunol Rev. 2008;226(1):205–18. doi: 10.1111/j.1600-065X.2008.00706.x.
  32. Kingo K, Ratsep R, Koks S, et al. Influence of genetic polymorphisms on interleukin-10 mRNA expression and psoriasis susceptibility. J Dermatol Sci. 2005;37(2):111–3. doi: 10.1016/j.jdermsci.2004.10.002.
  33. Howell MW. Interleukin-10 Gene Polymorphisms and Cancer. Madame Curie Bioscience Database [Internet]. Landes Bioscience; 2000–2013. Available from: (accessed 4.03.2021).
  34. Sabouri AH, Saito M, Lloyd AL, et al. Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J Infect Dis. 2004;190(7):1279–85. doi: 10.1086/423942.
  35. Zhang X, Hei P, Deng L, Lin J. Interleukin-10 gene promoter polymorphism and their protein production in peritoneal fluid in patients with endometriosis. Mol Hum Reprod. 2007;13(2):135–40. doi: 10.1093/molehr/gal106.

Role of TGF-b1 Gene Polymorphism in Development of Multiple Myeloma

AA Pavlova1, LN Bubnova1, YuV Sokolova1, EV Karyagina2, SS Bessmel’tsev1, IE Pavlova1

1 Russian Scientific Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For citation: Pavlova AA, Bubnova LN, Sokolova YuV, et al. Role of TGF-b1 Gene Polymorphism in Development of Multiple Myeloma. Clinical oncohematology. 2015;8(3):274–80 (In Russ).


Background & Aims. Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of the clonal plasma cells. Studies showed that the TGF-b1 cytokine induces growth of the tumor clone in MM. The aim of this study was to detect single nucleotide polymorphisms (SNP) of the TGF-b gene (codon 10, codon 25) associated with the development of MM and to determine risks of the bone disease development in residents of the Northwest Russia.

Methods. 43 patients with MM were examined (mean age: 69.2 ± 9.0 years). Patients were divided into two groups: the 1st group with severe osteolytic bone lesions and the 2nd one with signs of osteoporosis and solitary foci of lysis. The control group consisted of 40 healthy donors (mean age: 49.8 ± 10.1 years).

Results. The study demonstrated that MM was associated with TGF-b1 codon 25 CC genotype and TGF-b1 codon 10/codon 25 T/C haplotype. However, the TGF-b1 codon 25 GG genotype can be considered a marker of resistance to development of MM. Osteoporosis was associated with the TGF-b1 codon 25 GG genotype, whereas the TGF-b1 codon 25 GC was detected more frequently in patients with severe osteolytic bone lesions.

Conclusion. The obtained results indicate that individual genotypes and haplotypes of TGF-b1 are involved in the formation of predisposition to development of multiple myeloma.

Keywords: multiple myeloma, cytokines, TGF-b1, single nucleotide polymorphisms.

Received: February 9, 2015

Accepted: May 30, 2015

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  1. Бессмельцев С.С. Множественная миелома (патогенез, клиника, диагностика, дифференциальный диагноз). Часть I. Клиническая онкогематология. 2013;6(3):237–57.
    [Bessmel’tsev SS. Multiple myeloma (pathogenesis, clinical manifestations, diagnosis, differential diagnosis). Part I. Klinicheskaya onkogematologiya. 2013;6(3):237–57. (In Russ)]
  2. Черныш Н.Ю., Бессмельцев С.С., Козлов А.В. и др. Апоптотическая активность клеток костного мозга больных множественной миеломой. Вестник гематологии. 2009;5(3):5–11.
    [Chernysh NYu, Bessmel’tsev SS, Kozlov AV, et al. Apoptotic activity of bone marrow cells of patients with multiple myeloma. Vestnik gematologii. 2009;5(3):5–11. (In Russ)]
  3. Badros A. In the age of novel therapies, what defines high-risk multiple myeloma. J Natl Compr Canc Netw. 2010;8(Suppl 1):28–34.
  4. Свирновский А.И., Григорович С.А. Плейотропная резистентность опухолевых клеток к терапевтическим воздействиям при В-клеточных лимфопролиферативных заболеваниях. Медицинские новости. 2005;9:5–16.
    [Svirnovskii AI, Grigorovich SA. Pleiotropic resistance of tumor cells to therapeutic actions in B-cell lymphoproliferative disorders. Meditsinskie novosti. 2005;9:5–16. (In Russ)]
  5. Zheng C, Huang DR, Bergenbrant S, et al. Interleukin 6, tumour necrosis factor a, interleukin 1b and interleukin 1 receptor antagonist promoter or coding gene polymorphisms in multiple myeloma. Br J Haematol. 2000;109(1):39–45. doi: 10.1046/j.1365-2141.2000.01963.x.
  6. Atoum MF, Tanashat RQ, Mahmoud SA. Negative association of the HLA-DQB1*02 allele with breast cancer development among Jordanians. Asian Pacif J Cancer Prev. 2013;14(11):7007–10. doi: 10.7314/apjcp.2013.14.11.7007.
  7. Stern M, Opelz G, Dohler B, et al. Natural killer-cell receptor polymorphisms and posttransplantation non-Hodgkin lymphoma. Blood. 2010;115(19):3960–5. doi: 10.1182/blood-2009-10-250134.
  8. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation and cancer. J Clin Invest. 2007;117(5):1175–83. doi: 10.1172/jci31537.
  9. Landskron G, De la Fuente M, Thuwajit P, et al. Chronic inflammation and cytokines in the tumor microenvironment. J Immunol Res. 2014:149185. doi: 10.1155/2014/149185.
  10. Коненков В.И., Смольникова М.В. Структурные основы и функциональная значимость аллельного полиморфизма генов цитокинов человека и их рецепторов. Медицинская иммунология. 2003;5(1–2):11–28.
    [Konenkov VI, Smol’nikova MV. Structural matrix and functional significance of allelic polymorphism of human cytokine genes and their receptors. Meditsinskaya immunologiya. 2003;5(1–2):11–28. (In Russ)]
  11. Kekik C, Besisik S, Oguz FS, et al. Determination of cytokine gene polymorphisms in Turkish patients with multiple myeloma. Adv Mol Med. 2007;3(4):189–95.
  12. Ferrarini M, Mazzoleni G, Steimberg N, et al. Innovative models to assess multiple myeloma biology and the impact of drugs. In: Hajek R, ed. Multiple myeloma – a quick reflection on the fast progress. InTech; 2013. doi: 10.5772/54312.
  13. Yasui H, Hideshima T, Anderson KC. Inhibition of TGF-b Signaling in Multiple Myeloma and Its Bone Marrow Microenvironment. In: Jakowlew SB, ed. Transforming Growth Factor-b in Cancer Therapy. Vol. II. Springer; 2008. pp. 219–27. doi: 10.1007/978-1-59745-293-9_15.
  14. Павлова А.А., Павлова И.Е., Бессмельцев С.С. Цитокины и их роль в патогенезе множественной миеломы (Обзор литературы). 2013;14:313–35.
    [Pavlova AA, Pavlova IE, Bessmel’tsev SS. Cytokines and their role in pathogenesis of multiple myeloma (Literature review). 2013;14:313–35. (In Russ)]
  15. Buijs JT, Stayrook KR, Guise TA. The role of TGF-b in bone metastasis: novel therapeutic perspectives. BoneKey Rep. 2012;1(6):96. doi: 10.1038/bonekey.2012.96.
  16. Matsumoto T, Abe M. TGF-b-related mechanisms of bone destruction in multiple myeloma. Bone. 2011;48(1):129–34. doi: 10.1016/j.bone.2010.05.036.
  17. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors. 2004;22(4):233–41. doi: 10.1080/08977190412331279890.
  18. Mytilineos J, Laux G, Opelz G. Relevance of IL-10, TGF-b1, TNF-a and IL-4Ra gene polymorphisms in kidney transplantation: a collaborative transplant study report. Am J Transplant. 2004;4(10):1684–90. doi: 10.1111/j.1600-6143.2004.00561.x.
  19. Banu C, Moise A, Arion CV, et al. Cytokine gene polymorphisms support diagnostic monitoring of Romanian multiple myeloma patients. J Med Life. 2011;4(3):264–8.
  20. Brown EE, Lan Q, Zheng T, et al. Common variants in genes that mediate immunity and risk of multiple myeloma. Int J Cancer. 2007;120(12):2715–22. doi: 10.1002/ijc.22618.
  21. Барсова Р.М., Титов Б.В., Матвеева Н.А. и др. Участие гена TGFB1 в формировании предрасположенности к инфаркту миокарда. Acta Nat. 2012;4(2):76–82.
    [Barsova RM, Titov BV, Matveeva NA, et al. Involvement of the TGFB1 gene in predisposition to myocardial infarction. Acta Nat. 2012;4(2):76–82. (In Russ)]
  22. Blade J, Samson D, Reece D, et al. Criteria for evaluating disease response and progression in patients with multiple myeloma treated by high-dose therapy and haemopoietic stem cell transplantation. Myeloma Subcommittee of the EBMT. European Group for Blood and Marrow Transplantation. Br J Haematol. 1998;102(5):1115–23. doi: 10.1046/j.1365-2141.1998.00930.x.
  23. Durie BGM, Harousseau J-L, San-Miguel J, et al. International uniform response criteria for multiple myeloma. Leukemia. 2006;20(9):1467–73. doi: 10.1038/sj.leu.2404284.
  24. Бабышкина Н.Н., Малиновская Е.А., Стахеева М.Н. и др. Роль трансформирующего ростового фактора TGF-b1 в патогенезе рака молочной железы. Сибирский онкологический журнал. 2010;6(42):63–70.
    [Babyshkina NN, Malinovskaya EA, Stakheeva MN, et al. Role of transforming growth factor TGF-b1 in pathogenesis of breast cancer. Sibirskii onkologicheskii zhurnal. 2010;6(42):63–70. (In Russ)]
  25. Wrzesinnski SH, Wan YY, Flavell RA. Transforming growth factor-b and the immune response: implications for anticancer therapy. Clin Cancer Res. 2007;13(18):5262–70. doi: 10.1158/1078-0432.ccr-07-1157.