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Advances in immunopathogenesis of adult immune thrombocytopenia |
Xinguang Liu1, Yu Hou2, Jun Peng1( ) |
| 1. Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China; 2. Shandong University School of Medicine, Jinan, 250012, China |
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Abstract Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.
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| Keywords
primary immune thrombocytopenia
B lymphocytes
T lymphocytes
antigen-presenting cells
cytokines
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Corresponding Author(s):
Peng Jun,Email:junpeng88@sina.com.cn
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Issue Date: 05 December 2013
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| 1 |
Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, Chong BH, Cines DB, Gernsheimer TB, Godeau B, Grainger J, Greer I, Hunt BJ, Imbach PA, Lyons G, McMillan R, Rodeghiero F, Sanz MA, Tarantino M, Watson S, Young J, Kuter DJ. International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 2010; 115(2): 168-186
doi: 10.1182/blood-2009-06-225565 pmid:19846889
|
| 2 |
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, Bussel JB, Cines DB, Chong BH, Cooper N, Godeau B, Lechner K, Mazzucconi MG, McMillan R, Sanz MA, Imbach P, Blanchette V, Kühne T, Ruggeri M, George JN. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113(11): 2386-2393
doi: 10.1182/blood-2008-07-162503 pmid:19005182
|
| 3 |
Segal JB, Powe NR. Prevalence of immune thrombocytopenia: analyses of administrative data. J Thromb Haemost 2006; 4(11): 2377-2383
doi: 10.1111/j.1538-7836.2006.02147.x pmid:16869934
|
| 4 |
Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 2010; 85(3): 174-180
pmid:20131303
|
| 5 |
Terrell DR, Beebe LA, Neas BR, Vesely SK, Segal JB, George JN. Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol 2012; 87(9): 848-852
doi: 10.1002/ajh.23262 pmid:22674643
|
| 6 |
Harrington WJ, Sprague CC, Minnich V, Moore CV, Aulvin RC, Dubach R. Immunologic mechanisms in idiopathic and neonatal thrombocytopenic purpura. Ann Intern Med 1953; 38(3): 433-469
doi: 10.7326/0003-4819-38-3-433 pmid:13031392
|
| 7 |
Kiefel V, Freitag E, Kroll H, Santoso S, Mueller-Eckhardt C. Platelet autoantibodies (IgG, IgM, IgA) against glycoproteins IIb/IIIa and Ib/IX in patients with thrombocytopenia. Ann Hematol 1996; 72(4): 280-285
doi: 10.1007/s002770050173 pmid:8624385
|
| 8 |
Roark JH, Bussel JB, Cines DB, Siegel DL. Genetic analysis of autoantibodies in idiopathic thrombocytopenic purpura reveals evidence of clonal expansion and somatic mutation. Blood 2002; 100(4): 1388-1398
pmid:12149222
|
| 9 |
Gu D, Ge J, Du W, Xue F, Chen Z, Zhao H, Zhou Z, Xu J, Liu P, Zhao Q, Zhang L, Yang R. Raised expression of APRIL in Chinese patients with immune thrombocytopenia and its clinical implications. Autoimmunity 2009; 42(8): 692-698
doi: 10.3109/08916930903214025 pmid:19824872
|
| 10 |
Zhu XJ, Shi Y, Peng J, Guo CS, Shan NN, Qin P, Ji XB, Hou M. The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia. Blood 2009; 114(26): 5362-5367
doi: 10.1182/blood-2009-05-217513 pmid:19794139
|
| 11 |
Olsson B, Andersson PO, Jern?s M, Jacobsson S, Carlsson B, Carlsson LM, Wadenvik H. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9(9): 1123-1124
doi: 10.1038/nm921 pmid:12937414
|
| 12 |
Zhang F, Chu X, Wang L, Zhu Y, Li L, Ma D, Peng J, Hou M. Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura. Eur J Haematol 2006; 76(5): 427-431
doi: 10.1111/j.1600-0609.2005.00622.x pmid:16480433
|
| 13 |
Zhao C, Li X, Zhang F, Wang L, Peng J, Hou M. Increased cytotoxic T-lymphocyte-mediated cytotoxicity predominant in patients with idiopathic thrombocytopenic purpura without platelet autoantibodies. Haematologica 2008; 93(9): 1428-1430
pmid:18757854
|
| 14 |
Semple JW, Provan D. The immunopathogenesis of immune thrombocytopenia: T cells still take center-stage. Curr Opin Hematol 2012; 19(5): 357-362
doi: 10.1097/MOH.0b013e3283567541 pmid:22759631
|
| 15 |
Peng J, Liu C, Liu D, Ren C, Li W, Wang Z, Xing N, Xu C, Chen X, Ji C, Zhang M, Hou M. Effects of B7-blocking agent and/or CsA on induction of platelet-specific T-cell anergy in chronic autoimmune thrombocytopenic purpura. Blood 2003; 101(7): 2721-2726
doi: 10.1182/blood-2002-06-1666 pmid:12446456
|
| 16 |
Zhang XL, Peng J, Sun JZ, Guo CS, Yu Y, Wang ZG, Chu XX, Hou M. Modulation of immune response with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin-induced anergic T cells in chronic idiopathic thrombocytopenic purpura. J Thromb Haemost 2008; 6(1): 158-165
doi: 10.1111/j.1538-7836.2007.02804.x pmid:17944988
|
| 17 |
Zhu X, Zhu P, Guo XL. T cell repertoires correlate with pathogenesis of chronic idiopathic thrombocytopenic purpura.Natl Med J China (Zhonghua Yi Xue Za Zhi) 2005; 85(47): 3316-3322 (in Chinese)
pmid:16409835
|
| 18 |
Fogarty PF, Rick ME, Zeng W, Risitano AM, Dunbar CE, Bussel JB. T cell receptor VB repertoire diversity in patients with immune thrombocytopenia following splenectomy. Clin Exp Immunol 2003; 133(3): 461-466
doi: 10.1046/j.1365-2249.2003.02239.x pmid:12930375
|
| 19 |
Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, Han ZC. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 2005; 90(7): 914-923
pmid:15996929
|
| 20 |
Panitsas FP, Theodoropoulou M, Kouraklis A, Karakantza M, Theodorou GL, Zoumbos NC, Maniatis A, Mouzaki A. Adult chronic idiopathic thrombocytopenic purpura (ITP) is the manifestation of a type-1 polarized immune response. Blood 2004; 103(7): 2645-2647
doi: 10.1182/blood-2003-07-2268 pmid:14670926
|
| 21 |
Guo C, Chu X, Shi Y, He W, Li L, Wang L, Wang Y, Peng J, Hou M. Correction of Th1-dominant cytokine profiles by high-dose dexamethasone in patients with chronic idiopathic thrombocytopenic purpura. J Clin Immunol 2007; 27(6): 557-562
doi: 10.1007/s10875-007-9111-1 pmid:17619126
|
| 22 |
Zhang J, Ma D, Zhu X, Qu X, Ji C, Hou M. Elevated profile of Th17, Th1 and Tc1 cells in patients with immune thrombocytopenic purpura. Haematologica 2009; 94(9): 1326-1329
doi: 10.3324/haematol.2009.007823 pmid:19734430
|
| 23 |
Cao J, Li XQ, Chen C, Zeng LY, Cheng H, Li ZY, Pang XY, Xu KL. Imbalance of Th17/Treg cells ratio in peripheral blood of patients with immune thrombocytopenia. J Exp Hematol (Zhongguo Shi Yan Xue Ye Xue Za Zhi) 2011; 19(3): 730-733 (in Chinese)
pmid:21729560
|
| 24 |
Saitoh T, Tsukamoto N, Koiso H, Mitsui T, Yokohama A, Handa H, Karasawa M, Ogawara H, Nojima Y, Murakami H. Interleukin-17F gene polymorphism in patients with chronic immune thrombocytopenia. Eur J Haematol 2011; 87(3): 253-258
doi: 10.1111/j.1600-0609.2011.01651.x pmid:21615796
|
| 25 |
Rocha AM, Souza C, Rocha GA, de Melo FF, Clementino NC, Marino MC, Bozzi A, Silva ML, Martins Filho OA, Queiroz DM. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia. Haematologica 2011; 96(10): 1560-1564
doi: 10.3324/haematol.2011.046417 pmid:21972211
|
| 26 |
Cao J, Chen C, Zeng L, Li L, Li X, Li Z, Xu K. Elevated plasma IL-22 levels correlated with Th1 and Th22 cells in patients with immune thrombocytopenia. Clin Immunol 2011; 141(1): 121-123
pmid:21652269
|
| 27 |
Hu Y, Li H, Zhang L, Shan B, Xu X, Li H, Liu X, Xu S, Yu S, Ma D, Peng J, Hou M. Elevated profiles of Th22 cells and correlations with Th17 cells in patients with immune thrombocytopenia. Hum Immunol 2012; 73(6): 629-635
doi: 10.1016/j.humimm.2012.04.015 pmid:22537755
|
| 28 |
Cao J, Chen C, Li L, Zeng L, Li Z, Yan Z, Chen W, Cheng H, Sang W, Xu K. Effects of high-dose dexamethasone on regulating interleukin-22 production and correcting Th1 and Th22 polarization in immune thrombocytopenia. J Clin Immunol 2012; 32(3): 523-529
doi: 10.1007/s10875-012-9649-4 pmid:22289995
|
| 29 |
Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol 2008; 8(7): 523-532
doi: 10.1038/nri2343 pmid:18566595
|
| 30 |
Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, Cross R, Sehy D, Blumberg RS, Vignali DA. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450(7169): 566-569
doi: 10.1038/nature06306 pmid:18033300
|
| 31 |
Liu B, Zhao H, Poon MC, Han Z, Gu D, Xu M, Jia H, Yang R, Han ZC. Abnormality of CD4(+)CD25(+) regulatory T cells in idiopathic thrombocytopenic purpura. Eur J Haematol 2007; 78(2): 139-143
pmid:17328716
|
| 32 |
Ling Y, Cao X, Yu Z, Ruan C. Circulating dendritic cells subsets and CD4+Foxp3+ regulatory T cells in adult patients with chronic ITP before and after treatment with high-dose dexamethasome. Eur J Haematol 2007; 79(4): 310-316
doi: 10.1111/j.1600-0609.2007.00917.x pmid:17692100
|
| 33 |
Yu J, Heck S, Patel V, Levan J, Yu Y, Bussel JB, Yazdanbakhsh K. Defective circulating CD25 regulatory T cells in patients with chronic immune thrombocytopenic purpura. Blood 2008; 112(4): 1325-1328
doi: 10.1182/blood-2008-01-135335 pmid:18420827
|
| 34 |
Sakakura M, Wada H, Tawara I, Nobori T, Sugiyama T, Sagawa N, Shiku H. Reduced Cd4+Cd25+ T cells in patients with idiopathic thrombocytopenic purpura. Thromb Res 2007; 120(2): 187-193
doi: 10.1016/j.thromres.2006.09.008 pmid:17067661
|
| 35 |
Stasi R, Cooper N, Del Poeta G, Stipa E, Laura Evangelista M, Abruzzese E, Amadori S. Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab. Blood 2008; 112(4): 1147-1150
doi: 10.1182/blood-2007-12-129262 pmid:18375792
|
| 36 |
Bao W, Bussel JB, Heck S, He W, Karpoff M, Boulad N, Yazdanbakhsh K. Improved regulatory T-cell activity in patients with chronic immune thrombocytopenia treated with thrombopoietic agents. Blood 2010; 116(22): 4639-4645
doi: 10.1182/blood-2010-04-281717 pmid:20688957
|
| 37 |
Zhang XL, Peng J, Sun JZ, Liu JJ, Guo CS, Wang ZG, Yu Y, Shi Y, Qin P, Li SG, Zhang LN, Hou M. De novo induction of platelet-specific CD4(+)CD25(+) regulatory T cells from CD4(+)CD25(-) cells in patients with idiopathic thrombocytopenic purpura. Blood 2009; 113(11): 2568-2577
doi: 10.1182/blood-2008-03-148288 pmid:19056692
|
| 38 |
Shenoy S, Mohanakumar T, Chatila T, Tersak J, Duffy B, Wang R, Thilenius AR, Russell JH. Defective apoptosis in lymphocytes and the role of IL-2 in autoimmune hematologic cytopenias. Clin Immunol 2001; 99(2): 266-275
doi: 10.1006/clim.2001.5017 pmid:11318598
|
| 39 |
Olsson B, Andersson PO, Jacobsson S, Carlsson L, Wadenvik H. Disturbed apoptosis of T-cells in patients with active idiopathic thrombocytopenic purpura. Thromb Haemost 2005; 93(1): 139-144
pmid:15630504
|
| 40 |
Li X, Zhong H, Bao W, Boulad N, Evangelista J, Haider MA, Bussel J, Yazdanbakhsh K. Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood 2012; 120(16): 3318-3325
doi: 10.1182/blood-2012-05-432575 pmid:22859611
|
| 41 |
Mauri C, Bosma A. Immune regulatory function of B cells. Annu Rev Immunol 2012; 30(1): 221-241
doi: 10.1146/annurev-immunol-020711-074934 pmid:22224776
|
| 42 |
Geissmann F, Manz MG, Jung S, Sieweke MH, Merad M, Ley K. Development of monocytes, macrophages, and dendritic cells. Science 2010; 327(5966): 656-661
doi: 10.1126/science.1178331 pmid:20133564
|
| 43 |
Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002; 346(13): 995-1008
doi: 10.1056/NEJMra010501 pmid:11919310
|
| 44 |
Kuwana M, Okazaki Y, Ikeda Y. Splenic macrophages maintain the anti-platelet autoimmune response via uptake of opsonized platelets in patients with immune thrombocytopenic purpura. J Thromb Haemost 2009; 7(2): 322-329
doi: 10.1111/j.1538-7836.2008.03161.x pmid:18826388
|
| 45 |
Liu XG, Ma SH, Sun JZ, Ren J, Shi Y, Sun L, Dong XY, Qin P, Guo CS, Hou M, Peng J. High-dose dexamethasone shifts the balance of stimulatory and inhibitory Fcγ receptors on monocytes in patients with primary immune thrombocytopenia. Blood 2011; 117(6): 2061-2069
doi: 10.1182/blood-2010-07-295477 pmid:21131591
|
| 46 |
Asahi A, Nishimoto T, Okazaki Y, Suzuki H, Masaoka T, Kawakami Y, Ikeda Y, Kuwana M. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcγRIIB in immune thrombocytopenic purpura patients. J Clin Invest 2008; 118(8): 2939-2949
pmid:18654664
|
| 47 |
Wu Z, Zhou J, Prsoon P, Wei X, Liu X, Peng B. Low expression of FCGRIIB in macrophages of immune thrombocytopenia-affected individuals. Int J Hematol 2012; 96(5): 588-593
doi: 10.1007/s12185-012-1187-6 pmid:23054650
|
| 48 |
Hamzeh-Cognasse H, Cognasse F, Palle S, Chavarin P, Olivier T, Delézay O, Pozzetto B, Garraud O. Direct contact of platelets and their released products exert different effects on human dendritic cell maturation. BMC Immunol 2008; 9(1): 54
doi: 10.1186/1471-2172-9-54 pmid:18817542
|
| 49 |
Garcia-Suarez J, Prieto A, Reyes E, Manzano L, Merino JL, Alvarez-Mon M. Severe chronic autoimmune thrombocytopenic purpura is associated with an expansion of CD56+ CD3- natural killer cells subset. Blood 1993; 82(5): 1538-1545
pmid:7689873
|
| 50 |
Gernsheimer T. Chronic idiopathic thrombocytopenic purpura: mechanisms of pathogenesis. Oncologist 2009; 14(1): 12-21
doi: 10.1634/theoncologist.2008-0132 pmid:19144680
|
| 51 |
Van Wyk V, Kotzé HF, Heyns AP. Kinetics of indium-111-labelled platelets in HIV-infected patients with and without associated thrombocytopaenia. Eur J Haematol 1999; 62(5): 332-335
pmid:10359062
|
| 52 |
Ballem PJ, Segal GM, Stratton JR, Gernsheimer T, Adamson JW, Slichter SJ. Mechanisms of thrombocytopenia in chronic autoimmune thrombocytopenic purpura. Evidence of both impaired platelet production and increased platelet clearance. J Clin Invest 1987; 80(1): 33-40
doi: 10.1172/JCI113060 pmid:3597777
|
| 53 |
Jenkins JM, Williams D, Deng Y, Uhl J, Kitchen V, Collins D, Erickson-Miller CL. Phase 1 clinical study of eltrombopag, an oral, nonpeptide thrombopoietin receptor agonist. Blood 2007; 109(11): 4739-4741
doi: 10.1182/blood-2006-11-057968 pmid:17327409
|
| 54 |
Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, Nugent DJ. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 2003; 102(3): 887-895
doi: 10.1182/blood-2002-05-1475 pmid:12676790
|
| 55 |
McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004; 103(4): 1364-1369
doi: 10.1182/blood-2003-08-2672 pmid:14576051
|
| 56 |
Yang L, Wang L, Zhao CH, Zhu XJ, Hou Y, Jun P, Hou M. Contributions of TRAIL-mediated megakaryocyte apoptosis to impaired megakaryocyte and platelet production in immune thrombocytopenia. Blood 2010; 116(20): 4307-4316
doi: 10.1182/blood-2010-02-267435 pmid:20671119
|
| 57 |
Benedetti F, de Sabata D, Perona G. T suppressor activated lymphocytes (CD8+/DR+) inhibit megakaryocyte progenitor cell differentiation in a case of acquired amegakaryocytic thrombocytopenic purpura. Stem Cells 1994; 12(2): 205-213
doi: 10.1002/stem.5530120209 pmid:8199563
|
| 58 |
Li S, Wang L, Zhao C, Li L, Peng J, Hou M. CD8+ T cells suppress autologous megakaryocyte apoptosis in idiopathic thrombocytopenic purpura. Br J Haematol 2007; 139(4): 605-611
doi: 10.1111/j.1365-2141.2007.06737.x pmid:17979946
|
| 59 |
Cohen-Solal K, Villeval JL, Titeux M, Lok S, Vainchenker W, Wendling F. Constitutive expression of Mpl ligand transcripts during thrombocytopenia or thrombocytosis. Blood 1996; 88(7): 2578-2584
pmid:8839850
|
| 60 |
Kuter DJ. New thrombopoietic growth factors. Blood 2007; 109(11): 4607-4616
doi: 10.1182/blood-2006-10-019315 pmid:17289815
|
| 61 |
Gu J, Lu L, Xu R, Chen X. Plasma thrombopoietin levels in patients with aplastic anemia and idiopathic thrombocytopenic purpura. Chin Med J (Engl) 2002; 115(7): 983-986
pmid:12150725
|
| 62 |
von dem Borne A, Folman C, van den Oudenrijn S, Linthorst G, de Jong S, de Haas M. The potential role of thrombopoietin in idiopathic thrombocytopenic purpura. Blood Rev 2002; 16(1): 57-59
doi: 10.1054/blre.2001.0184 pmid:11913997
|
| 63 |
Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther 2004; 76(6): 628-638
doi: 10.1016/j.clpt.2004.08.010 pmid:15592334
|
| 64 |
Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet 2008; 371(9610): 395-403
doi: 10.1016/S0140-6736(08)60203-2 pmid:18242413
|
| 65 |
Erickson-Miller CL, DeLorme E, Tian SS, Hopson CB, Stark K, Giampa L, Valoret EI, Duffy KJ, Luengo JL, Rosen J, Miller SG, Dillon SB, Lamb P. Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist. Exp Hematol 2005; 33(1): 85-93
doi: 10.1016/j.exphem.2004.09.006 pmid:15661401
|
| 66 |
Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet 2009; 373(9664): 641-648
doi: 10.1016/S0140-6736(09)60402-5 pmid:19231632
|
| 67 |
Wang S, Yang R, Zou P, Hou M, Wu D, Shen Z, Lu X, Li Y, Chen X, Niu T, Sun H, Yu L, Wang Z, Zhang Y, Chang N, Zhang G, Zhao Y. A multicenter randomized controlled trial of recombinant human thrombopoietin treatment in patients with primary immune thrombocytopenia. Int J Hematol 2012; 96(2): 222-228
doi: 10.1007/s12185-012-1124-8 pmid:22753022
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