The etiology of acquired aplastic anemia

Reviews in Clinical and Experimental Hematology

Volumn 4, Issue 3, 2000, Pages 236-259

  Young, Neal S ^a  

^a NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BENZENE; GAMMA INTERFERON; HISTOCOMPATIBILITY ANTIGEN; INTERLEUKIN 2; TUMOR NECROSIS FACTOR;

APLASTIC ANEMIA; APOPTOSIS; CELL DESTRUCTION; CYTOTOXIC T LYMPHOCYTE; DISEASE ASSOCIATION; DISEASE CLASSIFICATION; DRUG EXPOSURE; HEMATOLOGIC DISEASE; HEMATOPOIETIC STEM CELL; HEPATITIS; HOST SUSCEPTIBILITY; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; MYELODYSPLASIA; PAROXYSMAL NOCTURNAL HEMOGLOBINURIA; PREGNANCY; REVIEW; STEM CELL; T LYMPHOCYTE ACTIVATION; TH1 CELL; VIRUS INFECTION;

EID: 0034261009     PISSN: 11270020     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1468-0734.2000.00017.x     Document Type: Review

References (111)

1. Keisu M and Young NS. Drugs and aplastic anemia. Eur J Haematol, 57 (Suppl.): 1, 2000.
2. Baranski B, Armstrong G, Truman JT, et al. Epstein-Barr virus in the bone marrow of patients with aplastic anemia. Ann Intern Med, 109: 695-704, 1988.
3. Tosato G, Taga K, Angiolillo A, et al. Epstein-Barr virus as an agent of haematological disease. In: Bailliére's Clinical Haematology, NS Young (ed.). Bailliére Tindall, London, pp. 165-199, 1995.
4. Brown KE, Tisdale J, Dunbar CE, et al. Hepatitis-associated aplastic anemia. N Engl J Med, 336: 1059-1064, 1997.
5. Kim SW, Rice L, Champlin R, et al. Aplastic anemia in eosinophilic fasciitis: Responses to immunosuppression and marrow transplantation. Haematologia, 28: 131-137, 1997.
6. Aitchison RGM, Marsh JCW, Hows JM, et al. Pregnancy associated aplastic anaemia: A report of five cases and review of current management. Br J Haematol, 73: 541-545, 1989.
7. van Besien K, Tricot G, Golichowski A, et al. Pregnancy-associated aplastic anemia - Report of 3 cases. Eur J Haematol, 47: 253-256, 1991.
8. Mathé G, Amiel JL, Schwarzenberg L, et al. Bone marrow graft in man after conditioning by antilymphocytic serum. Br Med J, 2: 131-136, 1970.
9. Young NS and Barrett AJ. The treatment of severe acquired aplastic anemia. Blood, 85: 3367-3377, 1995.
10. Frickhofen N and Rosenfeld SJ. Immunosuppressive treatment of aplastic anemia with antithymocyte globulin and cyclosporine. Semin Hematol, 37: 56-68, 2000.
11. Bacigalupo A, Bruno B, Saracco P, et al. Antilymphocyte globulin, cyclosporine, prednisolone, and granulocyte colony-stimulating factor for severe aplastic anemia: An update of the GITMO/EBMT study on 100 patients. European Group for Blood and Marrow Transplantation (EBMT) Working Party on Severe Aplastic Anemia and the Gruppo Italiano Trapianti di Midollo Osseo (GITMO). Blood, 95: 1931-1934, 2000.
12. Bacigalupo A, Oneto R, Bruno B, et al. Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Acta Haematol, 103: 19-25, 2000.
13. Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol, 159: 3-6, 1997.
14. Sloand E, Maciejewski JP, Kim S, et al. Pharmacologic doses of granulocyte colonystimulating factor affect cytokine production by lymphocytes in vitro and in vivo. Blood, 95: 2269-2274, 2000.
15. Issaragrisil S, Leaverton PE, Chansung K, et al. Regional patterns in the incidence of aplastic anemia in Thailand. Am J Hematol, 61: 164-168, 1999.
16. Chongli Y and Xiaobo Z. Incidence survey of aplastic anemia in China. Chin Med Sci J, 6: 203-207, 1991.
17. Kaufman DW, Kelly JP, Levy M, et al. The Drug Etiology of Agranulocytosis and Aplastic Anemia, Oxford University Press, New York, 1991.
18. Groves FD, Linet MS, Devesa SS. Epidemiology of human leukemia. Curr Opin Hematol, 1: 321-326, 1994.
19. Young NS. The epidemiology of blood diseases. In: Hematology 1999: American Society of Hematology Education Program Book, Schechter GP, Hoffman R, Schrier SL, et al. (eds). American Society of Hematology, Washington, DC, pp. 58-63, 1999.
20. Issaragrisil S, Kaufman DW, Anderson TE, et al. Low drug attributability of aplastic anemia in Thailand. Blood, 89: 4034-4039, 1997.
21. Issaragrisil S, Chansung K, Kaufman DW, et al. Aplastic anemia in rural Thailand: its association with grain farming and agricultural pesticide use. Am J Public Health, 87: 1551-1554, 1997.
22. Issaragrisil S, Kaufman D, Anderson T, et al. Association of seropositivity for hepatitis viruses and aplastic anemia in Thailand. Hepatology, 25: 1255-1257, 1997.
23. Issaragrisil S, Kaufman D, Piankijagum A, et al. High incidence of aplastic anemia in Bangkok is associated with low socioeconomic status and exposure to hepatitis [abstract]. Blood, 80 (Suppl. 1): 283A, 1992.
24. Vaquez MH and Aubertin C. L'anémie pernicieuse d'après les conceptions actuelles. Bull Mem Soc Med Hop Paris, 21: 288-297, 1904.
25. Maulopoulos L and Dimopoulos M. Magnetic resonance imaging of the bone marrow in hematologic malignancies. Blood, 90: 2127- 2147, 1997.
26. Maciejewski JP, Anderson S, Katevas P, et al. Phenotypic and functional analysis of bone marrow progenitor cell compartment in bone marrow failure. Br J Haematol, 87: 227-234, 1994.
27. Manz CY, Nissen C, Wodnar-Fillipowicz A. Deficiency of CD34+ c-kit+ and CD34+38-hematopoietic precursors in aplastic anemia after immunosuppressive treatment. Am J Hematol, 52: 264-274, 1996.
28. Otawa M, Kawanishi Y, Iwase O, et al. Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia. Leuk Res, 24: 359-366, 2000.
29. Scopes J, Bagnara M, Gordon-Smith EC, et al. Haemopoietic progenitor cells are reduced in aplastic anaemia. Br J Haematol, 86: 427-430, 1994.
30. Baciagalupo A, Piaggio G, Figari O, et al. Response of CFU-GM to increasing doses of rhGM-CSF in patients with aplastic anemia. Exp Hematol, 19: 829-832, 1991.
31. Aoki I, Higashi K, Homori M, et al. Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) in vitro in aplastic anemia and myelodysplastic syndrome. Am J Hematol, 35: 6-12, 1990.
32. Maciejewski JP, Selleri C, Sato T, et al. A severe and consistent deficit in marrow and circulating primitive hematopoietic cells (long term culture-initiating cells) in acquired aplastic anemia. Blood, 88: 1983-1991, 1996.
33. Schrezenmeier H, Jenal M, Herrmann F, et al. Quantitative analysis of cobblestone area-forming cells in bone marrow of patients with aplastic anemia by limiting dilution assay. Blood, 88: 4474-4480, 1996.
34. McManus PM and Weiss L. Busulfan-induced chronic bone marrow failure: Changes in cortical bone, marrow stromal cells, and adherent cell colonies. Blood, 64: 1036-1041, 1984.
35. Devetten MP and Young NS. Hematopoietic growth factors in the pathophysiology and treatment of aplastic anemia. In: Cytokines in the Treatment of Hematopoietic Failure, Hoelzer D and Ganseries A (eds). Marcel Dekker, New York City, 155-169, 1998.
36. Koijima S. Hematopoietic growth factors and marrow stroma in aplastic anemia. Int J Hematol, 68: 19-28, 1998.
37. Marsh JCW, Chang J, Testa NG, et al. In vitro assesssment of marrow 'stem cell' and stromal cell function in aplastic anaemia. Br J Haematol, 78: 258-267, 1991.
38. Novitzky N and Jacobs P. Immunosuppressive therapy in bone marrow aplasia: The stroma functions normally to support hematopoeisis. Exp Hematol, 23: 1472-1477, 1995.
39. Lyman SD, Seaberg M, Hanna R, et al. Plasma/serum levels of flt3 ligand are low in normal individuals and highly elevated in patients with Fanconi anemia and acquired aplastic anemia. Blood, 86: 4091-4096, 1995.
40. Kojima S, Matsuyama T, Kodera Y. Plasma levels and production of soluble stem cell factor by marrow stromal cells in patients with aplastic anaemia. Br J Haematol, 99: 440-446, 1997.
41. Li S, Champlin R, Fitchen JH, et al. Abnormalities of myeloid progenitor cells after 'successful' bone marrow transplantation. J Clin Invest, 75: 234-241, 1985.
42. Yoshida K, Miura I, Takahashi T, et al. Quantitative and qualitative analysis of stem cells of patients with aplastic anemia. Scand J Haematol, 30: 317-323, 1983.
43. Podesta M, Piaggio G, Frassoni F, et al. The assessment of the hematopoietic reservoir after immunosuppressive therapy or bone marrow transplantation in severe aplastic anemia. Blood, 91: 1959-1965, 1998.
44. Raghavachar A, Janssen JWG, Schrezenmeier H, et al. Clonal hematopoiesis as defined by polymorphic-X-linked loci occurs infrequently in aplastic anemia. Blood, 86: 2938-2947, 1995.
45. Abkowitz JL, Linenberger ML, Newton MA, et al. Evidence for the maintenance of hematopoiesis in a large animal by the sequential activation of stem-cell clones. Proc Natl Acad Sci USA, 87: 9062-9066, 1990.
46. Ball SE, Gibson FM, Rizzo S, et al. Progressive telomere shortening in aplastic anemia. Blood, 91: 3582-3592, 1998.
47. Brümmendorf TH, Maciejewski JP, Mak J, et al. Telomere length in peripheral blood cells of patients with bone marrow failure syndromes. Blood, in press: 2000.
48. Young NS. The problem of clonality in aplastic anemia. Dr. Dameshek's riddle, restated. Blood, 79: 1385-1392, 1992.
49. Gale RE and Wainscoat JS. Clonal analysis using X-linked DNA polymorphisms. Br J Haematol, 85: 2-8, 1993.
50. Notaro R, Cimmino A, Tabarini D, et al. In vivo telomere dynamics of human hematopoietic stem cells. Proc Natl Acad Sci USA, 94: 13782-13785, 1997.
51. Mortazavi Y, Tooze JA, Gordon-Smith EC, et al. N-RAS gene mutation in patients with aplastic anemia and aplastic anemia/paroxysmal nocturnal hemoglobinuria during evolution to clonal disease. Blood, 95: 646-650, 2000.
52. Piaggio G, Podestà M, Pitto A, et al. Coexistence of normal and clonal haemopoiesis in aplastic anaemia patients treated with immunosuppressive therapy. Br J Haematol, 107: 505-511, 1999.
53. Hattori H, Machii T, Ueda E, et al. Increased frequency of somatic mutations at glycophorin a loci in patients with aplastic anaemia, myelodysplastic syndrome and paroxysmal nocturnal haemoglobinuria. Br J Haematol, 98: 384-391, 1997.
54. Cahill DP, Lengauer C, Yu J, et al. Mutations of mitotic checkpoint genes in human cancers. Nature, 392: 300-303, 1998.
55. Kearns WG, Liu J, Aridgides L, et al. Genomic instability in bone marrow failure syndromes: High frequency of aneuploidy by fluorescence in situ hybridization and identification of a spindle checkpoint gene mutation. Blood, 94 (Suppl. 1): 674A, 1999 (Abstract).
56. Kagan WA, Ascensao JA, Pahwa RN, et al. Aplastic anemia: Presence in human bone marrow of cells that suppress myelopoiesis. Proc Natl Acad Sci USA, 73: 2890-2894, 1976.
57. Nakao S, Takami A, Takamatsu H, et al. Isolation of a T-cell clone showing HLA-DRB1 0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia. Blood, 89: 3691-3699, 1997.
58. Moebius U, Hermann F, Hercend T, et al. Clonal analysis of CD4+/CD8+ T cells in a patient with aplastic anemia. J Clin Invest, 87: 1567-1574, 1991.
59. Nakao S, Takamatsu H, Yachie A, et al. Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia. Exp Hematol, 23: 433-438, 1995.
60. Manz CY, Dietrich PY, Schnuriger V, et al. T-cell receptor chain variability in bone marrow and peripheral blood in severe acquired aplastic anemia. Blood Cells, Molecules, Diseases, 23: 110-122, 1997.
61. Zeng W, Nakano S, Takamatsu H, et al. Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: Evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia. Blood, 93: 3008-3016, 1999.
62. Gascon P, Zoumbos N, Young NS. An analysis of natural killer cells in aplastic anemia. Blood, 67: 1349-1355, 1986.
63. Myint AA, Malkovska V, Morgan S, et al. Antilymphocyte globulin therapy enhances impaired function of natural killer cells and lymphokine activated killer cells in aplastic anemia. Br J Haematol, 75: 578-584, 1990.
64. Bacigalupo A, Podestà M, Frassoni F, et al. Generation of CFU-C suppressor T cells in vitro V. A multistep process. Br J Haematol, 52: 421-427, 1982.
65. Zoumbos N, Djeu J, Young N. Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro. J Immunol, 133: 769-774, 1984.
66. Zoumbos N, Gascon P, Djeu J, et al. Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. Proc Natl Acad Sci USA, 82: 188-192, 1985.
67. Tong J, Bacigalupo A, Piaggio G, et al. In vitro response of T cells from aplastic anemia patients to antilymphocyte globulin and phytohemagglutinin: Colony-stimulating activity and lymphokine production. Exp Hematol, 19: 312-316, 1991.
68. Selleri C, Sato T, Anderson S, et al. Interferonγ and tumor necrosis factor-α suppress both early and late stages of hematopoiesis and induce programmed cell death. J Cell Physiol, 165: 538-546, 1995.
69. Nakao S, Yamaguchi M, Shiobara S. Interferon gamma gene expression in unstimulated bone marrow mononuclear cells predicts a response to cyclosporine therapy in aplastic anemia. Blood, 79: 2532-2535, 1992.
70. Nistico A and Young NS. Interferon gene expression in the bone marrow of patients with acquired aplastic anemia. Ann Intern Med, 120: 463-469, 1994.
71. Melenhorst JJ, van Krieken JHJM, Dreef E, et al. T cells selectively infiltrate bone marrow areas with residual haemopoiesis of patients with acquired aplastic anaemia. Br J Haematol, 99: 517-519, 1997.
72. Maciejewski JP, Hibbs JR, Anderson S, et al. Bone marrow and peripheral blood lymphocyte phenotype in patients with bone marrow failure. Exp Hematol, 22: 1102-1110, 1994.
73. Platanias L, Gascon P, Bielory L, et al. Lymphocyte subsets and lymphokines following anti-thymocyte globulin therapy in patients with aplastic anaemia. Br J Haematol, 66: 433-443, 1987.
74. Laver J, Castro-Malaspina H, Kernan NA, et al. In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: Correlation with granulomonopoietic inhibition in patients who respond to anti-thymocyte globulin. Br J Haematol, 69: 545-550, 1988.
75. Sloand E, Kim S, Maciejewski JP, et al. Presence of intracellular interferon-gamma (IFN-gamma) in circulating lymphocytes and response to immunosuppressive therapy in patients with aplastic anemia (Abstract). Blood, 10 (Suppl. 1): 158a, 1998.
76. Selleri C, Maciejewski JP, Sato T, et al. Interferon constitutively expressed in the stromal microenvironment of human marrow cultures mediates potent hematopoietic inhibition. Blood, 87: 4149-4157, 1996.
77. Maciejewski JP, Selleri C, Sato T, et al. Increased expression of Fas antigen on bone marrow CD34+ cells of patients with aplastic anemia. Br J Haematol, 91: 245-252, 1995.
78. Philpott NJ, Scopes J, Marsh JCW, et al. Increased apoptosis in aplastic anemia bone marrow progenitor cells: Possible pathophysiologic significance. Exp Hematol, 23: 1642-1648, 1995.
79. Maciejewski JP, Selleri C, Sato T, et al. Nitric oxide suppression of human hematopoiesis in vitro: Contribution to inhibitory action of interferon-γ and tumor necrosis factor-α. J Clin Invest, 96: 1085-1092, 1995.
80. Sato T, Selleri C, Young NS, et al. Inhibition of interferon regulatory factor-1 expression results in predominance of cell growth stimulatory effects of interferon-gamma due to phosphorylation of Stat1 and Stat3. Blood, 90: 4749-4758, 1997.
81. Wolk A, Simon-Stoos K, Nami I, et al. A mouse model of immune-mediated aplastic anemia (Abstract). Blood, 10 (Suppl. 1): 158a-159a, 1998.
82. Mori T, Nishimura T, Ikeda Y, et al. Involvement of Fas-mediated apoptosis in the hematopoietic progenitor cells of graft-versus-host reaction-associated myelosuppression. Blood, 92: 101-107, 1998.
83. Binder D, Van den Broek MF, Kagi D, et al. Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus (Abstract). J Exp Med, 187: 1903-1920, 1998.
84. Ehl S, Hombach J, Aichele P, et al. Bystander activation of cytotoxic T cells: Studies on the mechanism and evaluation of in vivo significance in a transgenic mouse model. J Exp Med, 185: 1241-1251, 1997.
85. Anderson KC and Weinstein HJ. Transfusion-associated graft-versus-host disease. N Engl J Med, 323: 315-321, 1990.
86. Fleischhauer K, Kernan NA, O'Reilly RJ, et al. Bone marrow-allograft rejection by T lymphocytes recognizing a single amino acid difference in HLA-B44. N Engl J Med, 323: 1818-1822, 1990.
87. Ito K, Yoshida H, Yanagibashi K, et al. Change of HLA phenotype in postoperative erythroderma. Lancet, 1: 413-414, 1988.
88. Stacey MW, Mcaninch T, Santi L, et al. Glutathione-S transferase (GSTT1 and GSTM1) null genotypes in patients with aplastic anemia and myelodysplastic syndromes (Abstract). Blood 94 (Suppl. 1): 675A, 1999.
89. Young NS. Agranulocytosis. In: The Bone Marrow Failure Syndromes, Young NS (ed). W.B. Saunders, Philadelphia, 156-182, 2000.
90. Nakao S, Takamatsu H, Chuhjo T, et al. Identification of a specific HLA class II haplotype strongly associated with susceptibility to cyclosporine-dependent aplastic anemia. Blood, 84: 4257-4261, 1994.
91. Molldrem J, Caples M, Mavroudis D, et al. Antithymocyte globulin (ATG) abrogates cytopenias in patients with myelodysplastic syndrome. Br J Haematol, 99: 699-705, 1997.
92. Jonasova A, Neuwirtova R, Cermak J, et al. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol, 200: 304-309, 1998.
93. Shetty V, Mundle S, Alvi S, et al. Measurement of apoptosis, proliferation and three cytokines in 46 patients with myelodysplastic syndromes. Leuk Res, 20: 891-900, 1996.
94. Molldrem JJ, Jiang YZ, Stetler-Stevenson M, et al. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br J Haematol, 102: 1314-1322, 1998.
95. Chapuis B, Von Fliedner VE, Jeannet M, et al. Increased frequency of DR2 in patients with aplastic anaemia and increased DR sharing in their parents. Br J Haematol, 63: 51-57, 1986.
96. Nimer SD, Ireland P, Meshkinpour A, et al. An increased HLA DR2 frequency is seen in aplastic anemia patients. Blood, 84: 923-927, 1994.
97. Lieberman JA, Yunis J, Egea E, et al. HLA-B38, DR4, DQw3 and clozapine-induced agranulocytosis in Jewish patients with schizophrenia. Arch Gen Psychiatr, 47: 945-948, 1990.
98. Tamai H, Sudo T, Kímura A, et al. Association between the DRB1*08032 histocompatibility antigen and methimazole-induced agranulocytosis in Japanese patients with Graves disease. Ann Intern Med, 124: 490-494, 1996.
99. McGuire W, Knight JC, Hill AV, et al. Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. J Infect Dis, 179: 287-290, 1999.
100. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, et al. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science, 286: 1957-1960, 1999.
101. Dunn DE, Tannawattanacharoen P, Boccuni P, et al. Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med, 131: 401-408, 1999.
102. Socie G, Rosenfeld S, Frickhofen N, et al. Late clonal diseases of treated aplastic anemia. Semin Hematol, 37: 91-101, 2000.
103. Kawagoe K, Kitamura D, Okabe M, et al. Glycosylphosphatidylinositol-anchor-deficient mice: Implications for clonal dominance of mutant cells in paroxysmal nocturnal hemoglobinuria. Blood, 87: 3600-3606, 1996.
104. Dunn DE, Yu J, Nagarajan S, et al. A knock-out model of paroxysmal nocturnal hemoglobinuria: PIG-A-hematopoiesis is reconstituted following intercellular transfer of gpi-anchored proteins. Proc Natl Acad Sci USA, 93: 7938-7943, 1996.
105. Hertenstein B, Wagner B, Bunjes D, et al. Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma. Blood, 86: 1487-1492, 1995.
106. Maciejewski JP, Sloand EM, Sato T, et al. Impaired hematopoiesis in paroxysmal nocturnal hemoglobinuria/aplastic anemia is not associated with a selective proliferative defect in the glycosylphosphatidylinositol-anchored protein-deficient clone. Blood, 89: 1173-1181, 1997.
107. Araten D, Nafa K, Pakdeesuwan K, et al. PNH cells and PIG-A gene mutations in normal donors (Abstract). Blood, 92 (Suppl. 1): 471a, 1998.
108. Hollander N, Selvaraj P, Springer TA. Biosynthesis and function of LFA-3 in human mutant cells deficient in phosphatidylinositol-anchored proteins. J Immunol, 141: 4283-4290, 1988.
109. Barrett AJ. Myelodysplastic syndrome and aplastic anemia: Distinct entities or diseases linked by a common pathophysiology? Semin Hematol, 37: 15-29, 2000.
110. Locasciulli A, Broccia G, Corda G, et al. Risk of cytogenetic abnormalities in patients with severe aplastic anemia receiving immunosuppression with or without G-CSF (Abstract). Bone Marrow Transplant, 23 (Suppl. 1): S30, 1999.
111. Nakamoto YG, Uidotti LG, Kuhlen CV, et al. Immune pathogenesis of hepatocellular carcinoma. J Exp Med, 188: 341-350, 1998.