Immune alterations in untreated and treated myelodysplastic syndrome

Expert Opinion on Drug Safety

Volumn 10, Issue 3, 2011, Pages 351-361

  Mewawalla, Prerna ^a   Dasanu, Constantin A ^b  

^a UNIVERSITY OF CONNECTICUT   (United States)

^b SAINT FRANCIS HOSPITAL AND MEDICAL CENTER   (United States)

Author keywords

autoimmunity; immune alterations defects; MDS therapy; myelodysplastic syndrome; T cell

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; AZACITIDINE; IMMUNOGLOBULIN; LENALIDOMIDE; RECOMBINANT ERYTHROPOIETIN; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RECOMBINANT GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; T LYMPHOCYTE RECEPTOR ALPHA CHAIN; T LYMPHOCYTE RECEPTOR BETA CHAIN; THALIDOMIDE;

AUTOIMMUNE DISEASE; AUTOIMMUNITY; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CYTOKINE PRODUCTION; CYTOTOXICITY; DENDRITIC CELL; DRUG MECHANISM; HUMAN; IMMUNE DEFICIENCY; IMMUNE FUNCTION TEST; MACROPHAGE; MONOCYTE; MYELODYSPLASTIC SYNDROME; NATURAL KILLER CELL; PATHOGENESIS; REGULATORY T LYMPHOCYTE; REVIEW;

ANIMALS; AUTOIMMUNITY; HUMANS; IMMUNE SYSTEM; MYELODYSPLASTIC SYNDROMES;

EID: 79955444925     PISSN: 14740338     EISSN: None     Source Type: Journal    
DOI: 10.1517/14740338.2011.534456     Document Type: Review

References (99)

1. Tefferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med 2009;10(19):1872-85
2. Nakagawa T, Saitoh S, Imoto S, et al. Multiple point mutation of N-ras and K-ras oncogenes in myelodysplastic syndrome and acute myelogenous leukemia. Oncology 1992;49:114
3. VanKamp H, DePijper C, Verlaan-de Vries M, et al. Longitudinal analysis of point mutations of the Nras protooncogene in patients with myelodysplasia using archival blood smears. Blood 1992;79:1266
4. Padua RA, Guinn BA, Al-Sabah AI, et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998;12:887
5. Raskind WH, Tirumali N, Jacobson R, et al. Evidence for a multistep pathogenesis of a myelodysplastic syndrome. Blood 1984;63(6):1318-23 (Pubitemid 14120375)
6. Greenberg PL. Apoptosis and its role in the myelodysplastic syndromes: implications for disease natural history and treatment. Leuk Res 1998;22:1123
7. Elghetany MT. Surface marker abnormalities in myelodysplastic syndromes. Haematologica 1998;83(12):1104-15
8. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and nonself. Nat Immunol 2005;6:345-52 (Pubitemid 41716771)
9. Huehn J, Hamann A. Homing to suppress: address codes for Treg migration. Trends Immunol 2005;26:632-6 (Pubitemid 41628195)
10. Miller MJ, Safrina O, Parker I, et al. Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. J Exp Med 2004;200:847-56 (Pubitemid 39362921)
11. Kordasti SY, Ingram W, Hayden J, et al. CD4+CD25+high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood 2007;110:847-50 .. A study clarifying the pivotal role of Tregs in the pathogenesis of MDS.
12. Kotsianidis I, Bouchliou I, Nakou E, et al. Kinetics, function and bone marrow trafficking of CD4+CD25 +FOXP3+regulatory T cells in myelodysplastic syndromes (MDS). Leukemia 2009;23(3):510-18
13. Zou JX, Rollison DE, Boulware D, et al. Altered naive and memory CD4+ T-cell homeostasis and immunosenescence characterize younger patients with myelodysplastic syndrome. Leukemia 2009;23(7):1288-96
14. Baumann I, Scheid C, Koref MS, et al. Autologous lymphocytes inhibit hemopoiesis in long-term cultures in patients with myelodysplastic syndromes. Exp Hematol 2002;30:1405-11 (Pubitemid 35452655)
15. Epperson DE, Nakamura R, Saunthararajah Y, et al. Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. Leuk Res 2001;25:1075-83 (Pubitemid 33000488)
16. Jonasova A, Neuwirtova R, Cermak J. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol 1998;200:304-9 (Pubitemid 28131061)
17. Tichelli A, Gratwohl A, Wuersch A, et al. Antilymphocyte globulin formyelodysplastic syndrome? Br J Haematol 1988;68:139-40
18. Biesma D, van den Tweel J, Verdonck L. Immunosuppressive therapy for hypoplastic myelodysplastic syndrome. Cancer 1997;79:1548-51 (Pubitemid 27154786)
19. Molldrem J, Caples M, Mavroudis D, et al. Antithymocyte globulin (ATG) abrogates cytopenias in patients with myelodysplastic syndrome. Br J Haematol 1997;99:699-705 (Pubitemid 27519877)
20. Wang XL, Shao ZH, Yao C, et al. Study of Th cell subsets in bone marrow of myelodysplastic syndromes patients. Zhonghua Xue Ye Xue Za Zhi 2005;26(12):743-5
21. Melenhorst JJ, Eniafe R, Follmann D, et al. Molecular and flow cytometric characterization of the CD4 and CD8 T-cell repertoire in patients with myelodysplastic syndrome. Br J Haematol 2002;119(1):97-105 (Pubitemid 35176503)
22. Matsutani T, Yoshioka T, Tsuruta Y, et al. Determination of T-cell receptors of clonal CD8-positive T-cells in myelodysplastic syndrome with erythroid hypoplasia. Leuk Res 2003;27:305-12 (Pubitemid 36071387)
23. Fozza C, Contini S, Galleu A, et al. Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4(+) subset and oligoclonal in the CD8(+) subset. Exp Hematol 2009;37(8):947-55
24. Gersuk GM, Lee JW, Beckham CA, et al. Fas (CD95) receptor and Fas-ligand expression in bone marrow cells from patients with myelodysplastic syndrome. Blood 1996;88:1122-3 (Pubitemid 26333341)
25. Shioi Y, Tamura H, Yokose N, et al. Increased apoptosis of circulating T cells in myelodysplastic syndromes. Leuk Res 2007;31(12):1641-8 (Pubitemid 350051398)
26. Matsutani T, Yoshioka T, Tsuruta Y, et al. Determination of T-cell receptors of clonal CD8-positive T-cells in myelodysplastic syndrome with erythroid hypoplasia. Leuk Res 2003;27(4):305-12 (Pubitemid 36071387)
27. Epperson DE, Nakamura R, Saunthararajah Y, et al. Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process. Leuk Res 2001;25(12):1075-83 (Pubitemid 33000488)
28. Yang J, Wang C, Xie KC, et al. Evaluation of the subsets of lymphocytes and their activated status in patients with myelodysplastic syndrome. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14(4):708-13
29. Molldrem JJ, Caples M, Mavroudis D, et al. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 1997;99:699
30. Jonasova A, Neuwirtova R, Cermak J, et al. Cyclosporine A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol 1998;100:304
31. Kochenderfer JN, Kobayashi S, Wieder ED, et al. Loss of T-lymphocyte clonal dominance in patients with myelodysplastic syndrome responsive to immunosuppression. Blood 2002;100(10):3639-45 (Pubitemid 35303934)
32. Plasilova M, Risitano A, Maciejewski JP. Application of the molecular analysis of the T-cell receptor repertoire in the study of immune-mediated hematologic diseases. Hematology 2003;8(3):173-81 (Pubitemid 36700702)
33. Hamdi W, Ogawara H, Handa H, et al. Clinical significance of Th1/Th2 ratio in patients with myelodysplastic syndrome. Int J Lab Hematol 2009;31(6):630-8
34. Kotsianidis I, Bouchliou I, Nakou E, et al. Kinetics, function and bone marrow trafficking of CD4+CD25 +FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS). Leukemia 2009;23(3):510-18
35. Kordasti SY, Afzali B, Lim Z, et al. IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Br J Haematol 2009;145(1):64-72
36. Amin HM, Jilani I, Estey EH, et al. Increased apoptosis in bone marrow B lymphocytes but not T lymphocytes in myelodysplastic syndrome. Blood 2003;102:1866
37. Katsuki K, Shinohara K, Kameda N, et al. Two cases of myelodysplastic syndrome with extramedullary polyclonal plasma cell proliferation and autoantibody production: possible role of soluble Fas antigen for production of excessive self-reactive B cells. Intern Med 1998;37(11):973-7 (Pubitemid 128520921)
38. Okamoto T, Okada M, Mori A, et al. Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients. Int J Hematol 1997;66(3):345-51 (Pubitemid 27495992)
39. Srivannaboon K, Conley ME, Coustan-Smith E, et al. Hypogammaglobulinemia and reduced numbers of B-cells in children with myelodysplastic syndrome. J Pediatr Hematol Oncol 2001;23(2):122-5 (Pubitemid 32162675)
40. Epling-Burnette PK, Bai F, Painter JS, et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood 2007;109(11):4816-24 (Pubitemid 46827777)
41. Marcondes AM, Mhyre AJ, Stirewalt DL, et al. Dysregulation of IL-32 in myelodysplastic syndrome and chronic myelomonocytic leukemia modulates apoptosis and impairs NK function. Proc Natl Acad Sci USA 2008;105(8):2865-70 (Pubitemid 351723635)
42. Kiladjian JJ, Bourgeois E, Lobe I, et al. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia 2006;20(3):463-70 (Pubitemid 43291745)
43. Orazi A, Milanesi B. The technicon H6000 automated hematology analyzer in the diagnosis and classification of the myelodysplastic syndromes. Haematologica 1990;75(1):87-90 (Pubitemid 20138544)
44. Jaworkowsky LI, Solovey DY, Rhausova LY, et al. Monocytosis as a sign of subsequent leukemia in patients with cytopenias (preleukemia). Folia Hematol (Frankf) 1983;110:395
45. Kitagawa M, Saito I, Kuwata T, et al. Overexpression of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma by bone marrow cells from patients with myelodysplastic syndromes. Leukemia 1997;11:2049-54 (Pubitemid 28043688)
46. Meers S, Kasran A, Boon L, et al. Monocytes are activated in patients with myelodysplastic syndromes and can contribute to bone marrow failure through CD40-CD40L interactions with T helper cells. Leukemia 2007;21(12):2411-19 (Pubitemid 350148882)
47. Kyriakou D, Liapi D, Kyriakou E, et al. Aberrant expression of the major sialoglycoprotein (CD43) on the monocytes of patients with myelodysplastic syndromes. Ann Hematol 2000;79(4):198-205 (Pubitemid 30224148)
48. Kufner S, Fleischer RP, Kroell T, et al. Serum-free generation and quantification of functionally active Leukemia-derived DC is possible from malignant blasts in acute myeloid leukemia and myelodysplastic syndromes. Cancer Immunol Immunother 2005;54(10):953-70 (Pubitemid 41199791)
49. Matteo Rigolin G, Howard J, Buggins A, et al. Phenotypic and functional characteristics of monocyte-derived dendritic cells from patients with myelodysplastic syndromes. Br J Haematol 1999;107(4):844-50 (Pubitemid 30020159)
50. Micheva I, Thanopoulou E, Michalopoulou S, et al. Defective tumor necrosis factor alpha-induced maturation of monocyte-derived dendritic cells in patients with myelodysplastic syndromes. Clin Immunol 2004;113(3):310-17 (Pubitemid 39422610)
51. Ma L, Ceuppens J, Kasran A, et al. Immature and mature monocyte-derived dendritic cells in myelodysplastic syndromes of subtypes refractory anemia or refractory anemia with ringed sideroblasts display an altered cytokine profile. Leuk Res 2007;31(10):1373-82 (Pubitemid 47212421)
52. Groupe Francaise de Morphologie Hematologique. French registry of acute leukemia and myelodysplastic syndromes. Cancer 1987; 60: 1385.
53. Shetty VT, Mundle SD, Raza A. Pseudo Pelger-Huet anomaly in myelodysplastic syndrome: hyposegmented or apoptotic neutrophil? Blood 2001;98:1273
54. Schofield KP, Stone PCW, Kelsey P, et al. Quantitative cytochemistry of blood neutrophils in myelodysplastic syndromes and chronic granulocytic leukaemia. Cell Biochem Funct 1983;1:92
55. Cech P, Markert M, Perrin LH. Partial myeloperoxidase deficiency in preleukemia. Blut 1983;47:21
56. Prodan M, Tulissi P, Perticarari S, et al. Flow cytometric assay for the evaluation of phagocytosis and oxidative burst of polymorphonuclear leukocytes and monocytes in myelodysplastic disorders. Haematologica 1995;80:212
57. Rose C, Wattel E, Bastion Y, et al. Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases. Leukemia 1994;8(9):1458-62 (Pubitemid 24293648)
58. Verhoef G, Boogaerts M. In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. Br J Haematol 1991;79:177-84
59. Shikama Y, Shichishima T, Ohto H, et al. Neutrophil-specific reduction in the expression of granulocyte-macrophage colony-stimulating factor receptor subunits in myelodysplastic syndromes. Br J Haematol 2000;111(3):863-72 (Pubitemid 32098924)
60. Clark RE, Smith SA, Jacobs A. Myeloid surface antigen abnormalities in myelodysplasia: relation to prognosis and modification by 13-cis retinoic acid. J Clin Pathol 1987;40:652
61. Ricevuti G, Mazzone A, Pasotti D, et al. The role of integrins in granulocyte dysfunction in myelodysplastic syndrome. Leuk Res 1993;17(7):609-19 (Pubitemid 23218270)
62. Peddie CM, Wolf CR, McLellan LI, et al. Oxidative DNA damage in CD34+ myelodysplastic cells is associated with intracellular redox changes and elevated plasma tumour necrosis factor-alpha concentration. Br J Haematol 1997;99:625-31 (Pubitemid 27519866)
63. Kordasti SY, Afzali B, Lim Z, et al. IL-17-producing CD4(+) T cells, pro-inflammatory cytokines and apoptosis are increased in low risk myelodysplastic syndrome. Br J Haematol 2009;145(1):64-72
64. Gritsaev SV, Rozanova OE, Abdulkadyrov KM, et al. Clinical significance of lymphocyte subpopulations and cytokine-producing activity of blood cells in patients with primary myelodysplastic syndrome. Vopr Onkol 2005;51(5):563-6
65. Ogata K, Tamura H, Yokose N, et al. Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-gamma and tumour necrosis factor-alpha in patients with myelodysplastic syndromes. Br J Haematol 1995;90(1):15-21
66. Barcellini W, Zaninoni A, Imperiali FG, et al. Anti-erythroblast autoimmunity in early myelodysplastic syndromes. Haematologica 2007;92(1):19-26 (Pubitemid 46232654)
67. Villaescusa Blanco R, Arce AA, Santos RM, et al. Changes of the complement system in myelodysplastic syndromes. Sangre (Barc) 1998;43(3):210-12 (Pubitemid 128519080)
68. Voulgarelis M, Giannouli S, Ritis K, et al. Myelodysplasia-associated autoimmunity: clinical and pathophysiologic concepts. Eur J Clin Invest 2004;34(10):690-700 (Pubitemid 39423027)
69. Dalamaga M, Lekka A, Karmaniolas K, et al. Is thyroid autoimmunity a risk factor for developing primary myelodysplastic syndrome? Cancer Causes Control 2008;19(4):371-8
70. Hamblin TJ. Immunological abnormalities in myelodysplastic syndromes. Semin Hematol 1996;33:150-62 (Pubitemid 26128722)
71. Saif MW, Hopkins JL, Gore SD. Autoimmune phenomena in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 2002;43(11):2083-92 (Pubitemid 35174719)
72. Enright H, Jacob HS, Vercellotti G, et al. Paraneoplastic autoimmune phenomena in patients with myelodysplastic syndromes: response to immunosuppressive therapy. Br J Haematol 1995;91:403-8
73. Castro M, Conn DL, Su WP, et al. Rheumatic manifestations in myelodysplastic syndromes. J Rheumatol 1991;18:721-7
74. Billstrom R, Johansson H, Johansson B, et al. Immune-mediated complications in patients with myelodysplastic syndromes - clinical and cytogenetic features. Eur J Haematol 1995;55:42-8
75. Okamoto T, Okada M, Mori A, et al. Correlation between immunological abnormalities and prognosis in myelodysplastic syndrome patients. Int J Hematol 1997;66:345-51 (Pubitemid 27495992)
76. Shah NM, Prajapati SG, Adesara RP, et al. An analysis of 30 cases of myelodysplastic syndrome. Indian J Pathol Microbiol 2009;52(2):206-9
77. Zhao S, Mao H, Wang H, et al. The relationship between myelodysplastic syndromes and autoimmune disorders. Zhonghua Xue Ye Xue Za Zhi 2002;23(6):311-13
78. Pfaffl W, Gross HJ, Neumeier D, et al. Lymphocyte subsets and delayed cutaneous hypersensitivity in hemodialysis patients receiving recombinant human erythropoietin. Contrib Nephrol 1988;66:195-204
79. Mann RA, Jetzt AE, Singh M, et al. The effect of erythropoietin administration on murine bone marrow chimeras. Immunol Lett 1996;49:15-20 (Pubitemid 26101254)
80. Birmingham DJ, Shen XP, Hartman JA, et al. Effect of chronic human recombinant erythropoietin therapy on antibody responses to immunization in chronic hemodialysis patients. Kidney Int 1996;50:543-9 (Pubitemid 26274383)
81. Prutchi-Sagiv S, Golishevsky N, Oster HS, et al. Erythropoietin treatment in advanced multiple myeloma is associated with improved immunological functions: could it be beneficial in early disease? Br J Haematol 2006;135(5):660-72 (Pubitemid 44674077)
82. Katz O, Gil L, Lifshitz L, et al. Erythropoietin enhances immune responses in mice. Eur J Immunol 2007;37(6):1584-93 (Pubitemid 46939493)
83. Han S, Song Y, Lee YH, et al. Macrophage-colony stimulating factor enhances MHC-restricted presentation of exogenous antigen in dendritic cells. Cytokine 2005;32(5):187-93 (Pubitemid 43144649)
84. Chitta S, Santambrogio L, Stern LJ. GMCSF in the absence of other cytokines sustains human dendritic cell precursors with T-cell regulatory activity and capacity to differentiate into functional dendritic cells. Immunol Lett 2008;116(1):41-54
85. List A, Dewald G, Bennett J, et al.; Myelodysplastic Syndrome-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355(14):1456-65 (Pubitemid 44511560)
86. Chanan-Khan AA, Cheson BD. Lenalidomide for the treatment of B-cell malignancies. J Clin Oncol 2008;26:1544-52
87. Muller GW, Chen R, Huang SY, et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett 1999;9(11):1625-30 (Pubitemid 29274209)
88. Mchugh SM, Rifkin IR, Deighton J, et al. The immunosuppressive drug thalidomide induces T helper cell type 2 (Th2) and concomitantly inhibits Th1 cytokine production in mitogen- and antigen-stimulated human peripheral blood mononuclear cell cultures. Clin Exp Immunol 1995;99(2):160-7
89. Menon S, Habermann T, Witzig T. Lenalidomide-associated hypothyroidism. Leuk Lymphoma 2007;48:2465-7 (Pubitemid 350253484)
90. Deng A, Harvey V, Sina B, et al. Interstitial granulomatous dermatitis associated with the use on tumor necrosis factor alpha inhibitors. Arch Dermatol 2006;142(2):198-202 (Pubitemid 43276531)
91. Dasanu CA, Alexandrescu DT. A case of severe aplastic anemia secondary to treatment with lenalidomide for multiple myeloma. Eur J Haematol 2009;82(3):231-4
92. Sekeres MA, Schoonen WM, Kantarjian H, et al. Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst 2008;100:1542-51
93. Jones PA, Taylor SM, Wilson VL. Inhibition of DNA methylation by 5-azacytidine. Recent Results Cancer Res 1983;84:202-11
94. Jiang Y, Dunbar A, Gondek LP, et al. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood 2009;113(6):1315-25
95. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 2009;10:223-32
96. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794-803
97. Kantarjian H, Oki Y, Garcia-Manero G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:52-7 (Pubitemid 46053042)
98. Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol 2009;27:3842-8
99. Sanchez-Abarca LI, Gutierrez-Cosio S, Santamaria C, et al. Immunomodulatory effect of 5-azacytidine (5-azaC): potential role in the transplantation setting. Blood 2010;115(1):107-21