Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Oct;76(4):1391–1397. doi: 10.1172/JCI112115

Definition of a possible genetic basis for susceptibility to acute myelogenous leukemia associated with the presence of a polymorphic Ia epitope.

S Seremetis, J Cuttner, R Winchester
PMCID: PMC424083  PMID: 2414320

Abstract

The polymorphic Ia epitope recognized by monoclonal antibody 109d6 is detectable on the leukemic cells of a significantly increased number of individuals with acute myelogenous leukemia, compared with its frequency in normal healthy control individuals. In control individuals, the presence of the 109d6 epitope is closely correlated with but not identical to the DRw53 allo-specificity. However, the frequency of particular conventional Ia allodeterminants, including DRw53, is not significantly elevated in the leukemia group. Considerable evidence supports the conclusion that the high frequency of the 109d6 epitope reflects an inherited basis for susceptibility to the development of acute myelogenous leukemia and not a differentiation event occurring in the leukemic lineage. The 109d6 determinant is expressed by leukemic myeloblasts as well as by homologous normal B cells and monocytes obtained from the same individuals during remission of the leukemia. Furthermore, in healthy family members the 109d6 epitope is encoded by Ia haplotypes that are shared with the patient. Of special interest, certain of these haplotypes have combinations of the 109d6 epitope and Ia specificities not commonly seen in normal individuals; here, also, healthy family members share these haplotypes.

Full text

PDF
1391

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auffray C., Korman A. J., Roux-Dosseto M., Bono R., Strominger J. L. cDNA clone for the heavy chain of the human B cell alloantigen DC1: strong sequence homology to the HLA-DR heavy chain. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6337–6341. doi: 10.1073/pnas.79.20.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball E. D., Fanger M. W. The expression of myeloid-specific antigens on myeloid leukemia cells: correlations with leukemia subclasses and implications for normal myeloid differentiation. Blood. 1983 Mar;61(3):456–463. [PubMed] [Google Scholar]
  3. Bennett J. M., Catovsky D., Daniel M. T., Flandrin G., Galton D. A., Gralnick H. R., Sultan C. Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol. 1976 Aug;33(4):451–458. doi: 10.1111/j.1365-2141.1976.tb03563.x. [DOI] [PubMed] [Google Scholar]
  4. Bernstein I. D., Andrews R. G., Cohen S. F., McMaster B. E. Normal and malignant human myelocytic and monocytic cells identified by monoclonal antibodies. J Immunol. 1982 Feb;128(2):876–881. [PubMed] [Google Scholar]
  5. Billing R., Rafizadeh B., Drew I., Hartman G., Gale R., Terasaki P. Human B-lymphocyte antigens expressed by lymphocytic and myelocytic leukemia cells. I. Detection by rabbit antisera. J Exp Med. 1976 Jul 1;144(1):167–178. doi: 10.1084/jem.144.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bollum F. J. Terminal deoxynucleotidyl transferase as a hematopoietic cell marker. Blood. 1979 Dec;54(6):1203–1215. [PubMed] [Google Scholar]
  7. Burmester G. R., Yu D. T., Irani A. M., Kunkel H. G., Winchester R. J. Ia+ T cells in synovial fluid and tissues of patients with rheumatoid arthritis. Arthritis Rheum. 1981 Nov;24(11):1370–1376. doi: 10.1002/art.1780241106. [DOI] [PubMed] [Google Scholar]
  8. Böyum A. Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl. 1968;97:77–89. [PubMed] [Google Scholar]
  9. Chromosomes in acute non-lymphocytic leukaemia. First International Workshop on Chromosomes in Leukaemia. Br J Haematol. 1978 Jul;39(3):311–316. doi: 10.1111/j.1365-2141.1978.tb01103.x. [DOI] [PubMed] [Google Scholar]
  10. Cuttner J., Seremetis S., Najfeld V., Dimitriu-Bona A., Winchester R. A. TdT-positive acute leukemia with monocytoid characteristics: clinical, cytochemical, cytogenetic, and immunologic findings. Blood. 1984 Jul;64(1):237–243. [PubMed] [Google Scholar]
  11. D'Amaro J., Bach F. H., Van Rood J. J., Rimm A. A., Bortin M. M. HLA C associations with acute leukaemia. Lancet. 1984 Nov 24;2(8413):1176–1178. doi: 10.1016/s0140-6736(84)92741-7. [DOI] [PubMed] [Google Scholar]
  12. Daly P. A., Simon R., Schiffer C. A., Aisner J., Terasaki P. I., Wiernik P. H. A study of HLA antigens and haplotypes in a population of Caucasians with acute non-lymphocytic leukemia. Leuk Res. 1979;3(2):75–82. doi: 10.1016/0145-2126(79)90065-1. [DOI] [PubMed] [Google Scholar]
  13. Dimitriu-Bona A., Burmester G. R., Waters S. J., Winchester R. J. Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol. 1983 Jan;130(1):145–152. [PubMed] [Google Scholar]
  14. Falkenburg J. H., Jansen J., van der Vaart-Duinkerken N., Veenhof W. F., Blotkamp J., Goselink H. M., Parlevliet J., van Rood J. J. Polymorphic and monomorphic HLA-DR determinants on human hematopoietic progenitor cells. Blood. 1984 May;63(5):1125–1132. [PubMed] [Google Scholar]
  15. Foon K. A., Schroff R. W., Gale R. P. Surface markers on leukemia and lymphoma cells: recent advances. Blood. 1982 Jul;60(1):1–19. [PubMed] [Google Scholar]
  16. Giles R. C., Nunez G., Hurley C. K., Nunez-Roldan A., Winchester R., Stastny P., Capra J. D. Structural analysis of a human I-A homologue using a monoclonal antibody that recognizes an MB3-like specificity. J Exp Med. 1983 May 1;157(5):1461–1470. doi: 10.1084/jem.157.5.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gonwa T. A., Picker L. J., Raff H. V., Goyert S. M., Silver J., Stobo J. D. Antigen-presenting capabilities of human monocytes correlates with their expression of HLA-DS, an Ia determinant distinct from HLA-DR. J Immunol. 1983 Feb;130(2):706–711. [PubMed] [Google Scholar]
  18. Gorski J., Rollini P., Long E., Mach B. Molecular organization of the HLA-SB region of the human major histocompatibility complex and evidence for two SB beta-chain genes. Proc Natl Acad Sci U S A. 1984 Jul;81(13):3934–3938. doi: 10.1073/pnas.81.13.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goyert S. M., Silver J. Further characterization of HLA-DS molecules: implications for studies assessing the role of human Ia molecules in cell interactions and disease susceptibility. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5719–5723. doi: 10.1073/pnas.80.18.5719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hurley C. K., Giles R. C., Nunez G., DeMars R., Nadler L., Winchester R., Stastny P., Capra J. D. Molecular localization of human class II MT2 and MT3 determinants. J Exp Med. 1984 Aug 1;160(2):472–493. doi: 10.1084/jem.160.2.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hurley C. K., Nunez G., Winchester R., Finn O. J., Levy R., Capra J. D. The human HLA-DR antigens are encoded by multiple beta-chain loci. J Immunol. 1982 Nov;129(5):2103–2108. [PubMed] [Google Scholar]
  22. KAPLOW L. S. SIMPLIFIED MYELOPEROXIDASE STAIN USING BENZIDINE DIHYDROCHLORIDE. Blood. 1965 Aug;26:215–219. [PubMed] [Google Scholar]
  23. LILLY F., BOYSE E. A., OLD L. J. GENETIC BASIS OF SUSCEPTIBILITY TO VIRAL LEUKAEMOGENESIS. Lancet. 1964 Dec 5;2(7371):1207–1209. doi: 10.1016/s0140-6736(64)91043-8. [DOI] [PubMed] [Google Scholar]
  24. Martin P. J., Najfeld V., Fialkow P. J. B-lymphoid cell involvement in chronic myelogenous leukemia: implications for the pathogenesis of the disease. Cancer Genet Cytogenet. 1982 Aug;6(4):359–368. doi: 10.1016/0165-4608(82)90092-9. [DOI] [PubMed] [Google Scholar]
  25. McCulloch E. A. The blast cells of acute myeloblastic leukaemia. Clin Haematol. 1984 Jun;13(2):503–515. [PubMed] [Google Scholar]
  26. Nunez-Roldan A., Szer I., Toguchi T., Cuttner J., Winchester R. Association of certain Ia allotypes with the occurrence of chronic lymphocytic leukemia. Recognition by a monoclonal anti-Ia reagent of a susceptibility determinant not in the DR series. J Exp Med. 1982 Dec 1;156(6):1872–1877. doi: 10.1084/jem.156.6.1872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nuñez G., Giles R. C., Ball E. J., Hurley C. K., Capra J. D., Stastny P. Expression of HLA-DR, MB, MT and SB antigens on human mononuclear cells: identification of two phenotypically distinct monocyte populations. J Immunol. 1984 Sep;133(3):1300–1306. [PubMed] [Google Scholar]
  28. Oliver R. T., Pillai A., Klouda P. T., Lawler S. D. HLA linked resistance factors and survival in acute myelogenous leukemia. Cancer. 1977 Jun;39(6):2337–2341. doi: 10.1002/1097-0142(197706)39:6<2337::aid-cncr2820390603>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  29. Schlossman S. F., Chess L., Humphreys R. E., Strominger J. L. Distribution of Ia-like molecules on the surface of normal and leukemic human cells. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1288–1292. doi: 10.1073/pnas.73.4.1288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Spielman R. S., Lee J., Bodmer W. F., Bodmer J. G., Trowsdale J. Six HLA-D region alpha-chain genes on human chromosome 6: polymorphisms and associations of DC alpha-related sequences with DR types. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3461–3465. doi: 10.1073/pnas.81.11.3461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomson G. A review of theoretical aspects of HLA and disease associations. Theor Popul Biol. 1981 Oct;20(2):168–208. doi: 10.1016/0040-5809(81)90009-5. [DOI] [PubMed] [Google Scholar]
  32. Todd R. F., 3rd, Nadler L. M., Schlossman S. F. Antigens on human monocytes identified by monoclonal antibodies. J Immunol. 1981 Apr;126(4):1435–1442. [PubMed] [Google Scholar]
  33. Toguchi T., Burmester G., Nunez-Roldan A., Gregersen P., Seremetis S., Lee S., Szer I., Winchester R. Evidence for the separate molecular expression of four distinct polymorphic Ia epitopes on cells of DR4 homozygous individuals. Hum Immunol. 1984 Jun;10(2):69–81. doi: 10.1016/0198-8859(84)90074-0. [DOI] [PubMed] [Google Scholar]
  34. Trowsdale J., Lee J., Carey J., Grosveld F., Bodmer J., Bodmer W. Sequences related to HLA-DR alpha chain on human chromosome 6: restriction enzyme polymorphism detected with DC alpha chain probes. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1972–1976. doi: 10.1073/pnas.80.7.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ulmer A. J., Flad H. D. Discontinuous density gradient separation of human mononuclear leucocytes using Percoll as gradient medium. J Immunol Methods. 1979;30(1):1–10. doi: 10.1016/0022-1759(79)90268-0. [DOI] [PubMed] [Google Scholar]
  36. Waters S. J., Winchester R. J., Nagase F., Thorbecke G. J., Bona C. A. Antigen presentation by murine and human cells to a murine T-cell hybridoma: demonstration of a restriction element associated with a major histocompatibility complex class II determinant(s) shared by both species. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7559–7563. doi: 10.1073/pnas.81.23.7559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Winchester R. J., Ross G. D., Jarowski C. I., Wang C. Y., Halper J., Broxmeyer H. E. Expression of Ia-like antigen molecules on human granulocytes during early phases of differentiation. Proc Natl Acad Sci U S A. 1977 Sep;74(9):4012–4016. doi: 10.1073/pnas.74.9.4012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Winchester R. J., Wang C. Y., Halper J., Hoffman T. Studies with B-cell allo- and hetero-antisera: parallel reactivity and special properties. Scand J Immunol. 1976;5(6-7):745–757. doi: 10.1111/j.1365-3083.1976.tb03024.x. [DOI] [PubMed] [Google Scholar]
  39. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]
  40. Yam L. T., Li C. Y., Lam K. W. Tartrate-resistant acid phosphatase isoenzyme in the reticulum cells of leukemic reticuloendotheliosis. N Engl J Med. 1971 Feb 18;284(7):357–360. doi: 10.1056/NEJM197102182840704. [DOI] [PubMed] [Google Scholar]
  41. von Fliedner V. E., Sultan-Khan Z., Jeannet M. HLA-DRw antigens associated with acute leukemia. Tissue Antigens. 1980 Nov;16(5):399–404. doi: 10.1111/j.1399-0039.1980.tb00321.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES