Clonal Variation, Autoimmunity, and Neoplasia: An Ecology Lesson from Paroxysmal Nocturnal Hemoglobinuria
Authors: Edward J. Benz
Journal: Annals of Internal Medicine (1999)

Editorials21 September 1999Clonal Variation, Autoimmunity, and Neoplasia: An Ecology Lesson from Paroxysmal Nocturnal HemoglobinuriaEdward J. Benz Jr., MDEdward J. Benz Jr., MDJohns Hopkins University School of Medicine; Baltimore, MD 21205 (Benz)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-6-199909210-00013 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The immune response is regarded as one line of host defense against cancer. Thus, cancer seen in immunodeficient states is attributed to loss of immune surveillance, and immune augmentation strategies for anticancer therapy are strenuously pursued. In this issue, Dunn and colleagues (1) propose that immune attack might actually confer an ecological advantage on some neoplastic cells in their microenvironment. They suggest that the distinctive neoplastic clones encountered in patients with paroxysmal nocturnal hemoglobinuria (PNH) may gain the upper hand only in bone marrow affected by autoimmune destruction of normal clones. Much additional work will be required to test this ...References1. Dunn DE, Tanawattanacharoen P, Boccuni P, Nagakura S, Green SW, Kirby MR, et al . Paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure syndromes. Ann Intern Med. 1999;131:401-8. LinkGoogle Scholar2. Rosse WF. Paroxysmal nocturnal hemoglobinuria as a molecular disease. Medicine (Baltimore). 1997; 76:63-93. Google Scholar3. Ham TH, Dingle JH. Studies on destruction of red blood cells. II. Chronic hemolytic anemia with paroxysmal nocturnal hemoglobinuria: certain immunological aspects of the hemolytic mechanism with special reference to serum complement. J Clin Invest. 1938;18:657. CrossrefGoogle Scholar4. Young NS. The problem of clonality in aplastic anemia. Dr. Dameshek's riddle, restated. Blood. 1992;79:1385-92. CrossrefMedlineGoogle Scholar5. Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997;336:1365-72. CrossrefMedlineGoogle Scholar6. Kinoshita T, Inoue N, Takeda J. Role of phosphatidylinositol-linked proteins in paroxysmal nocturnal hemoglobinuria pathogenesis. Annu Rev Med. 1996;47:1-10. CrossrefMedlineGoogle Scholar7. Rosse WF, Ware RE. The molecular basis of paroxysmal nocturnal hemoglobinuria. Blood. 1995;86:3277-86. CrossrefMedlineGoogle Scholar8. Brodsky RA, Vala MS, Barber JP, Medof ME, Jones RJ. Resistance to apoptosis caused by PIG-A gene mutations in paroxysmal nocturnal hemoglobinuria. Proc Natl Acad Sci U S A. 1997;94:8756-60. CrossrefMedlineGoogle Scholar9. Ware RE, Nishimura J, Moody MA, Smith C, Rosse WF, Howard TA. The PIG-A mutation and absence of glycosylphosphatidylinositol-linked proteins do not confer resistance to apoptosis in paroxysmal nocturnal hemoglobinuria. Blood. 1998;92:2541-50. CrossrefMedlineGoogle Scholar10. Dunn DE, Nagakura S, Tanawattanacharoen P, Knez J, Medof ME, Young NS. The PNH phenotype (GPI-anchored protein-deficiency) protects hematopoietic targets against lymphocytotoxic attack [Abstract]. Blood. 1997;90:407a. MedlineGoogle Scholar11. Araten DJ, Nafa K, Pakdeesuwan K, Luzzatto L. Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria genotype and phenotype are present in normal individuals. Proc Natl Acad Sci U S A. 1999;96:5209-14. CrossrefMedlineGoogle Scholar12. Rotoli B, Luzzatto L. Paroxysmal nocturnal haemoglobinuria. Baillieres Clin Haematol. 1989;2:113-38. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Edward J. BenzJr., MDAffiliations: Johns Hopkins University School of Medicine; Baltimore, MD 21205 (Benz)Corresponding Author: Edward J. Benz Jr., MD, Johns Hopkins University School of Medicine, Room 926, 1830 East Monument Street, Baltimore, MD 21205. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoParoxysmal Nocturnal Hemoglobinuria Cells in Patients with Bone Marrow Failure Syndromes Daniel E. Dunn , Patcharin Tanawattanacharoen , Piernicola Boccuni , Shoichi Nagakura , Spencer W. Green , Martha R. Kirby , Mysore S. Anil Kumar , Stephen Rosenfeld , and Neal S. Young Metrics Cited byMonoclonal constitution of neutrophils detected by PCR-based human androgen receptor gene assay in a subset of idiopathic thrombocytopenic purpura patientsIdiopathic thrombocytopenic purpura and myelodysplastic syndrome: distinct entities or overlapping syndromes? 21 September 1999Volume 131, Issue 6Page: 467-468KeywordsAplastic anemiaBone marrowCellsEcologyHemoglobinMembrane proteinsOuter membrane proteinsPhenotypesProteinsSomatic mutation ePublished: 15 August 2000 Issue Published: 21 September 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...