Immunobiology of Lymphoid Malignancy

  • M. F. Greaves
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 28)


The study of ‘membrane markers’ in human leukaemia has now been in progress for a decade. Starting from the initial observation of L. Borella and colleagues at St. Judes on the sub-types of ALL [1] a wealth of data has accumulated particularly over the past few years with the introduction of monoclonal antibodies. Now is perhaps a good time to appraise the impact of these efforts and the implications for future research on leukaemia.


Acute Lymphoblastic Leukaemia Lymphoid Malignancy Leukaemic Cell Maturation Arrest Phoblastic Leukaemia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Sen L, Borella L (1975) Clinical importance of lymphoblasts with T markers in childhood acute leukemia. N Engl J Med 292:828–832PubMedCrossRefGoogle Scholar
  2. 2.
    Fialkow PJ, Denman AM, Singer J, Jacobson RJ, Lowenthal MN (1978) Human myeloproliferative disorders: clonal origin in pluripotential stem cells. In: Clarkson B, Marks PA, Till JE (eds) Differentiation of normal and neoplastic hemopoietic cells. Cold Spring Harbor, New York, pp 131–144Google Scholar
  3. 3.
    Greaves MF (1982) ‘Target’ cells, cellular phenotypes and lineage fidelity in human leukaemia. J Cell Physiol Suppl 1: 113–126CrossRefGoogle Scholar
  4. 4.
    Greaves MF (1981) Analysis of the clinical and biological significance of lymphoid phenotypes in acute leukemia. Cancer Res 41:4752–4766PubMedGoogle Scholar
  5. 5.
    Dow LW, Borella L, Sen L, Aur RJA, George SL, Mauer AM, Simone JV (1977) Initial prognostic factors and lymphoblast-erythrocyte rosette formation in 109 children with acute lymphoblastic leukemia. Blood 50:671–682PubMedGoogle Scholar
  6. 6.
    Greaves MF, Janossy G, Peto J, Kay H (1981) Immunologically defined subclasses of acute lymphoblastic leukaemia in children: their relationship to presentation features and prognosis. Br J Haematol 48: 179–197PubMedGoogle Scholar
  7. 7.
    Janossy G, Bollum FJ, Bradstock KF, Ashley J (1980) Cellular phenotypes of normal and leukemic hemopoietic cells determined by analysis with selected antibody combinations. Blood 56:430–441PubMedGoogle Scholar
  8. 8.
    Reinherz EL, Kung PC, Goldstein G, Levey RH, Schlossman SF (1980) Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T lineage. Proc Natl Acad Sci USA 77: 1588–1592PubMedCrossRefGoogle Scholar
  9. 9.
    Greaves MF, Delia D, Robinson J, Sutherland R, Newman R (1981) Exploitation of monoclonal antibodies: A ‘Who’s who’ of haemopoietic malignancy. Blood Cells 7:257–280PubMedGoogle Scholar
  10. 10.
    Greaves, MF, Rao J, Hariri G, Verbi W, Catovsky D, Kung P, Goldstein G (1981) Phenotypic heterogeneity and cellular origins of T-cell malignancies. Leukemia Res 5:281–299CrossRefGoogle Scholar
  11. 11.
    Greaves MF (1981) Monoclonal antibodies as probes for leukaemic heterogeneity and haemopoietic differentiation. In: Knapp W (ed) Leukemia markers. Academic, New York, pp 19–32Google Scholar
  12. 12.
    Greaves MF, Paxton A, Janossy G, Pain C, Johnson S, Lister TA (1980) Acute lymphoblastic leukaemia associated antigen. III. Alterations in expression during treatment and in relapse. Leukemia Res 4: 1–14CrossRefGoogle Scholar
  13. 13.
    Greaves MF, Robinson JB, Delia D, Ritz J, Schlossman S, Sieff C, Goldstein G, Kung P, Bollum F, Edwards P (1981) Comparative antigenic phenotypes of normal and leukemic hemopoietic precursor cells analysed with a ‘library’ of monoclonal antibodies. In: Neth R, Gallo RC, Graf T, Mannweiler K, Winkler K (eds) Modern trends in human leukemia 4. Springer, Berlin Heidelberg New York, pp 296–304 (Haematology and blood transfusion, vol 26)Google Scholar
  14. 13a.
    Greaves MF (to be published) Subtypes of acute lymphoblastic leukaemia: implications for the pathogenesis and epidemiology of leukaemia. In: Magrath I, Ramot B (eds) The influence of the environment on leukaemia and lymphoma subtypes. Natl Cancer Inst MonogrGoogle Scholar
  15. 14.
    Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves MF (1981) Ubiquitous, cell surface glycoprotein on tumour cells is proliferation-associated receptor for transferrin. Proc Natl Acad Sci USA 78:4515–4519PubMedCrossRefGoogle Scholar
  16. 15.
    Potter VR (1978) Phenotypic diversity in experimental hepatomas: the concept of partially blocked ontogeny. Br J Cancer 38: 1–23PubMedCrossRefGoogle Scholar
  17. 16.
    Bradstock KF, Janossy G, Bollum FJ, Milstein C (1980) Anomalous gene expression in human thymic acute lymphoblastic leukaemia (Thy-ALL). Nature 284:455–457PubMedCrossRefGoogle Scholar
  18. 17.
    Greaves MF, Verbi W, Vogler L, Cooper M, Ellis R, Ganeshaguru K, Hoflbrand V, Janossy G, Bollum FJ (1979) Antigenic and enzymatic phenotypes of the pre-B subclass of acute lymphoblastic leukaemia. Leukemia Res 3:353–362CrossRefGoogle Scholar
  19. 18.
    Greaves MF (1982) ‘Target’ cells, differentiation and clonal evolution in chronic granulocytic leukaemia: A ‘model’ for understanding the biology of malignancy. In: Shaw MT (ed) Chronic granulocytic leukaemia. Praeger, New York, pp 15–47Google Scholar
  20. 19.
    Greaves MF (1981) Biology of acute lymphoblastic leukaemia. 16th Annual Guest Lecture: Leukaemia Research Fund Pub IGoogle Scholar
  21. 20.
    Greaves MF, Bell R, Amess J, Lister TA (to be published) What is ‘undifferentiated’ leukaemia?Google Scholar
  22. 21.
    Magrath IT, Ziegler JL (1980) Bone marrow involvement in Burkitt-s lymphoma and its relationship to acute B-cell leukemia. Leukemia Res 4:33–60CrossRefGoogle Scholar
  23. 22.
    Greaves MF, Sieff C, Edwards P (1983) Monoclonal anti-glycophorin as a probe for erythroleukaemias. Blood (in press)Google Scholar
  24. 23.
    Nagasawa K, Mak TW (1980) Phorbol esters induce differentiation in human malignant T lymphoblasts. Proc Natl Acad Sci USA 77:2964–2968PubMedCrossRefGoogle Scholar
  25. 24.
    Delia D, Greaves M, Newman R, Sutherland R, Minowada J, Kung P, Goldstein G (1982) Modulation of T leukaemic cell phenotype with phorbol ester. Int J Cancer 29:23–31PubMedCrossRefGoogle Scholar
  26. 25.
    Greaves MF, Janossy G (1978) Patterns of gene expression and the cellular origins of human leukaemia. Biochim Biophys Acta 516: 193–230PubMedGoogle Scholar
  27. 26.
    Greaves MF (1979) Tumour markers, phenotypes and maturation arrest in malignancy: A cell selection hypothesis. In Boelsma E, Rümke P (eds) Tumour markers. Elsevier, Amsterdam, pp 201–211Google Scholar
  28. 27.
    Varmus H (1982) Recent evidence for oncogenesis by insertion mutagenesis and gene activation. In: Greaves M (ed) Leukaemia cell differentiation. Cancer Surveys, vol 2. ICRF, London, pp 309–320Google Scholar
  29. 28.
    Schneider C, Sutherland R, Newman R, Greaves M (1982) Structural features of the cell surface receptor for transferrin that is recognised by the monoclonal antibody OKT9. J Biol Chem 251: 8516–8522Google Scholar
  30. 29.
    Goodfellow PN, Banting G, Sutherland R, Greaves M, Solomon E, Povey S (1982) Expression of the human transferrin receptor is controlled by a gene on chromosome 3: assignment using the species specificity of a monoclonal antibody. Somatic Cell Genet 8: 197–206PubMedCrossRefGoogle Scholar
  31. 30.
    Vodinelich L, Sutherland DR, Schneider C, Newman R, Greaves MF (1983) The receptor for transferrin may be a ‘target’ structure for natural killer cells. Proc Natl Acad Sci (in press)Google Scholar
  32. 31.
    Ritz J, Pesando JM, Notis-McConarty J, Lazarus H, Schlossman SF (1980) A monoclonal antibody to human acute lymphoblastic leukaemia antigen. Nature 283: 583–585PubMedCrossRefGoogle Scholar
  33. 32.
    Sutherland R, Smart J, Niaudet P, Greaves MF (1978) Acute lymphoblastic associated antigen. II. Isolation and partial characterization. Leukemia Res 2: 115–126CrossRefGoogle Scholar
  34. 33.
    Newman RA, Sutherland R, Greaves MF (1981) The biochemical characterization of a cell surface antigen associated with acute lymphoblastic leukemia and lymphocyte precursors. J Immunol 126:2024–2030PubMedGoogle Scholar
  35. 34.
    Kersey JH, LeBien TW, Abramson CS, Newman R, Sutherland R, Greaves M (1981) p24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody. J Exp Med 153:726–731PubMedCrossRefGoogle Scholar
  36. 35.
    Newman RA, Sutherland DR, LeBien TW, Kersey JH, Greaves MF (1982) Biochemical characterization of a leukaemia-associated antigen (p24) defined by the monoclonal antibody BA-2. Biochim Biophys Acta 701:318–327PubMedCrossRefGoogle Scholar
  37. 36.
    Newman R, Greaves MF (1982) Characterisation of HLA-DR on leukaemic cells. Clin Exp Immunol 50:41–50PubMedGoogle Scholar
  38. 37.
    Terhorst C, Van Agthovan A, LeClair K, Snow P, Reinherz E, Schlossman S (1981) Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. Cell 23:771–780PubMedCrossRefGoogle Scholar
  39. 38.
    Verbi W, Greaves MF, Schneider C, Koubek K, Janossy G, Stein H, Kung P, Goldstein G (1982) Monoclonal antibodies OKT10 and OKT11A have pan T reactivity and block sheep erythrocyte ‘receptors’. Eur J Immunol 12:81–86PubMedCrossRefGoogle Scholar
  40. 39.
    Brodsky FM, Parham P, Barnstable CJ, Crumpton M, Bodmer WF (1979) Hybrid myeloma monoclonal antibodies against MHC products. Immunol Rev 47:3–61PubMedCrossRefGoogle Scholar
  41. 40.
    Vogler LB, Crist WM, Bockman DE, Pearl ER, Lawton AR, Cooper MD (1978) Pre-B cell leukemia: a new phenotype of childhood lymphoblastic leukemia. N Engl J Med 298: 872–878PubMedCrossRefGoogle Scholar
  42. 41.
    Korsmeyer SJ, Hieter PA, Ravetch, JV, Poplack DG, Waldmann TA, Leder P (1981) Developmental hierarchy of immunoglobulin gene rearrangements in human leukemic pre-B cells. Proc Natl Acad Sci USA 78:7096–7100PubMedCrossRefGoogle Scholar
  43. 42.
    Dewji N, Rapson N, Greaves M, Ellis R (1981) Isoenzyme profiles of lysosomal hydrolases in leukaemic cells. Leukemia Res 5: 19–27CrossRefGoogle Scholar
  44. 43.
    Reddy EP, Reynolds RK, Santos E, Barbacid M (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300: 149–152PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1983

Authors and Affiliations

  • M. F. Greaves

There are no affiliations available

Personalised recommendations