Skip to main content
SpringerLink
Log in

Classification of patients with T-cell chronic lymphocytic leukemia and expansions of granular lymphocytes: Heterogeneity of Italian cases by a multiparameter analysis

  • Original Articles
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

The peripheral blood mononuclear cells (PBMC) from 750 Italian patients with chronic lymphocytic leukemia (CLL) were evaluated in order to detect cases with T-cell expansions. The PBMC of 18 patients (2.4%) were found to be capable of rosetting with sheep red blood cells. Further characterization of these cells with a panel of monoclonal antibodies and other immunological and cytochemical tests led us to tentatively subdivide these 18 patients into three groups. The first one included 6 patients whose cells expressed a T-helper phenotype: they exhibited frequent skin involvement and an aggressive clinical course, and some of the patients in this group demonstrated chromosome abnormalities. On the other hand, group 2 (10 cases with expansions of granular lymphocytes and/or T suppressor-bearing phenotype cells) usually presented with a mild clinical course. These cases did not generally require therapy and a diagnosis of leukemia could not be univocally confirmed. Cells from the two remaining patients displayed both B-cell markers and E-rosetting ability, thus belonging to the rare group of false T-cell CLL. In fact, the clinical course and management of the latter cases were similar to those of classical B-CLL disease. In the first and second groups, mechanisms reported to be involved in mature T-cell proliferations (response to interleukin-2, production of interleukin-2 or interferon) were investigated, but the cells under study displayed neither growth ability nor lymphokine production in the above assays. In addition, these cells were negative with the anti-Tac monoclonal antibody that appears to recognize the receptor for interleukin-2. More importantly, none of these patients had serum antibodies to the recently described human T-cell leukemia/lymphoma virus (HTLV), possibly responsible for Japanese and West Indian adult T-cell leukemia (ATL) and for sporadic cases of ATL observed in other countries. Taken together, our results outline some differences between European and ATL patients. Furthermore, the data presented point out the heterogeneity of the disease and emphasize that an immunological classification and, in particular, the detection of a helper phenotype have relevant prognostic and therapeutical importance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aisenberg AC, Bloch KJ: Immunoglobulins on the surface of neoplastic lymphocytes. N Engl J Med 287:271–276, 1972

    Google Scholar 

  2. Salsano F, Fröland SS, Natvig JB, Michaelson TE: Same idiotype of B lymphocyte membrane IgD and IgM. Formal evidence for monoclonality of chronic lymphocytic leukemia cells. Scand J Immunol 3:841–846, 1974

    Google Scholar 

  3. Jondal M, Holm G, Wigzell H: Surface markers on human T and B lymphocytes. J Exp Med 136:207–212, 1972

    Google Scholar 

  4. Aiuti F, Wigzell H: Function and distribution pattern of human T lymphocytes. Clin Exp Immunol 13:171–176, 1973

    Google Scholar 

  5. Aisenberg AC: Cell surface markers in lymphoproliferative diseases. N Engl J Med 13:331–335, 1981

    Google Scholar 

  6. Brouet JC, Flandrin G, Sasportes M, Preud'homme JL: Chronic lymphocytic leukemia of T-cell origin: Immunological and clinical evaluation in eleven patients. Lancet 2:890–893, 1975

    Google Scholar 

  7. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino M: Adult T-cell leukemia: Clinical and hematologic features of 16 cases. Blood 50:481–492, 1977

    Google Scholar 

  8. Robert-Guroff M, Nakao Y, Notake K, Ito Y, Sliski A, Gallo RC: Natural antibodies to human retrovirus HTLV in a cluster of Japanese patients with adult T cell leukemia. Science 215:975, 1982

    Google Scholar 

  9. Hattori T, Uchiyama T, Toibana T, Takatsuki K, Uchino H: Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies. Blood 58:645–647, 1981

    Google Scholar 

  10. Catovsky D, Greaves MF, Rose M, Galton DAG, Goolden AWG, McCluskey DR, White JM, Lampert I, Bourikas G, Ireland R, Brownwell AI, Bridges JM, Blattner WA, Gallo RC: Adult T-cell lymphoma-leukaemia in Blacks from the West Indies. Lancet 1:639–643, 1982

    Google Scholar 

  11. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack RS: Clinical staging of chronic lymphocytic leukemia. Blood 46:219–234, 1975

    Google Scholar 

  12. Pandolfi F, De Rossi G, Semenzato G, Quinti I, Ranucci A, De Sanctis G, Lopez M, Gasparotto G, Aiuti F: Immunologic evaluation of T chronic lymphocytic leukemia cells: Correlations among phenotype, functional activities, and morphology. Blood 59:688–695, 1982

    Google Scholar 

  13. Reinherz EL, Schlossman SF: Regulation of the immune response. N Engl J Med 303:370–373, 1980

    Google Scholar 

  14. Abo T, Balch CM: A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029, 1981

    Google Scholar 

  15. Ortaldo JR, Sharrow SO, Timonen T, Herberman RB: Determination of surface antigens of highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol 127:2401–2409, 1981

    Google Scholar 

  16. Leonard WJ, Depper JM, Uchiyama T, Smith KA, Waldmann TA, Greene WC: A monoclonal antibody that appears to recognize the receptor for human T-cell grow factor; Partial characterization of the receptor. Nature 300:267–268, 1982

    Google Scholar 

  17. Haynes BF, Metzgar RS, Minna JD, Bunn PA: Phenotypic characterization of cutaneous T-cell lymphoma. N Engl J Med 304:1319–1323, 1981

    Google Scholar 

  18. Semenzato G, Amadori G, Basso G, Cocito MB, Colombatti M, Anglani F, Gasparotto G: Immunological features in chronic lymphocytic leukemia (CLL) of T cell origin. J Clin Lab Immunol 2:45–60, 1979

    Google Scholar 

  19. Pandolfi F, Strong DM, Slease RB, Smith ML, Ortaldo JR, Herberman RB: Characterization of a suppressor T-cell chronic lymphocytic leukemia with ADCC but not NK activity. Blood 56:653–660, 1980

    Google Scholar 

  20. Pandolfi F, Semenzato G, De Rossi G, Strong DM, Quinti I, Pezzutto A, Mandelli F, Aiuti F: Heterogeneity of T-CLL defined by monoclonal antibodies in nine patients. Clin Immunol Immunopathol 24:330–341, 1983

    Google Scholar 

  21. Pandolfi F, Quinti I, De Rossi G, Frielingsdorf A, Tonietti G, Pasqualetti D, Aiuti F: A population of sheep rosetting cells lacking T- and monocytic-specific antigens, as detected by monoclonal antibodies. Clin Immunol Immunopathol 22:331–339, 1982

    Google Scholar 

  22. Pandolfi F, Semenzato G, De Rossi G, Quinti I, Guglielmi C, Pezzutto A, Lopez M, Tonietti G, Fontana L, Abo T, Aiuti F: HNK-1 monoclonal antibody (Leu 7) in the identification of abnormal expansions of large granular lymphocytes. Clin Exp Immunol 52:691–697, 1983

    Google Scholar 

  23. Moretta L, Webb SR, Grossi CE, Lydyart PM, Cooper MD: Functional analysis of two human T cell subpopulations: Help and suppression of B cell response by T cells bearing receptors for IgM and IgG, J Exp Med 146:185–201, 1977

    Google Scholar 

  24. Timonen T, Ortaldo JR, Herberman RB: Characterization of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 143:568–583, 1981

    Google Scholar 

  25. Semenzato G, Pizzolo G, Gerosa F, Pandolfi F, Pezzutto A, Andrighetto GC, Quinti I, Agostini C, Foa R, Tridente G: Binding of sheep erythrocytes in chronic lymphocytic leukemia of B cell origin. J Clin Immunol 2:296–302, 1983

    Google Scholar 

  26. Lutzner MA, Jordan HW: The ultrastructure of an abnormal cell in Sézary's syndrome. Blood 31:719–726, 1968

    Google Scholar 

  27. Pandolfi F, Blattner WA, De Rossi G, Semenzato G, Strong DM, Gallo RC: T-cell leukaemia-lymphoma virus and heterogeneity of chronic T-cell malignancies. Lancet 2:1273, 1982

    Google Scholar 

  28. Gallo RC, Wong-Staal F: Retroviruses as etiologic agents of some animal and human leukemias and lymphomas and as tools for elucidating the molecular mechanism of leukemogenesis. Blood 60:545–557, 1982

    Google Scholar 

  29. Gallo RC, Kalynaraman VS, Sarngadharan MG, Sliski A, Vonderheid EC, Maeda M, Nakao Y, Yamada K, Yohei I: Association of the human type C retrovirus with a subset of adult T-cell cancers. Cancer Res 43:3892–3899, 1983

    Google Scholar 

  30. Rümke HC, Miedema F, Berge IJMT, Terpstra F, Reijeden HJv, Griend RJv, DeBruin HG, Dem Borne AEGKv, Smit JW, Zeijlemaker WP, Melief CJM: Functional properties of T cells in patients with chronic Tγ lymphocytosis and chronic T cell neoplasia. J Immunol 129:419–426, 1982

    Google Scholar 

  31. Aisenberg AC, Wilkes BM, Harris NL, Koh HK: T-cell chronic lymphocytic leukemia. Report of a case studied with monoclonal antibody. Am J Med 72:695–699, 1982

    Google Scholar 

  32. Chilosi M, Pizzolo G, Semenzato G, De Rossi G, Pandolfi F: Heterogeneous expression of dypeptidyl-amino-peptidase (DAP IV) in T-cell chronic lymphocytic leukemia. Acta Haematol (in press), 1984

  33. Bom-Van Boorloos AA, Pegels HG, Rein MD, Van Ders RH, Silberbusch J, Feltkamp-Vroom TM, Goudsmit R, Sejlemaker WP, Von Dem Bourne AEGK, Melief CJM: Proliferation of Tγ cells with killer-cell activity in two patients with neutropenia and recurrent infections. N Engl J Med 302:933–937, 1980

    Google Scholar 

  34. Aisenberg AC, Wilkes BM, Harris NL, Ault KA, Carey RW: Chronic T-cell lymphocytosis with neutropenia: Report of a case studied with monoclonal antibodies. Blood 58:818–822, 1981

    Google Scholar 

  35. Callard RE, Smith CM, Worman C, Linch D, Cawley JC, Beverly PCL: Unusual phenotype and function of an expanded subpopulation of T cells in patients with hematopoietic disorders. Clin Exp Immunol 43:497–505, 1981

    Google Scholar 

  36. Andre C, Farcet JP, Oudhriri N, Gouerdin MF, Bouguet J, Reyes F: Phenotype study with monoclonal antibodies of T lymphocyte colonies in normal individuals and in patients with chronic OKT8+ lymphocytic leukemia. Clin Exp Immunol 54:515–524, 1983

    Google Scholar 

  37. Strong DM, Pandolfi F, Slease RB, Budd JE, Woody JN: Antigenic characterization of a T-CLL with heteroantisera and monoclonal antibodies. Evidence for the T-cell lineage of an Ia positive, Fc-IgG positive, suppressor cell subpopulation. J Immunol 162:205–208, 1981

    Google Scholar 

  38. Gramatski M, Pandolfi F, Maples JA, De Rossi G, Semenzato G, Quinti I, Schumacher HR, Bonnard GD, Strong DM: Interleukin-2 response in T-cell CLL and hand mirror ALL: In nine cases the cultured T-cells appear to be an outgrowth of normal cells. J Cancer Res Clin Oncol 105:A40, 1983

    Google Scholar 

  39. Hooks JJ, Haynes BF, Detrick-Hooks B, Deihl LF, Gerrard TL, Fauci A: Gamma (immune) interferon production by leukocytes from a patient with TG cell proliferative disease. Blood 59:198–201, 1982

    Google Scholar 

  40. Itoh K, Tsuchikawa K, Awataguchi T, Shiiba K, Kumagai K: A case of chronic lymphocytic leukemia with properties characteristic of natural killer cells. Blood 61:940–948, 1983

    Google Scholar 

  41. Cummer CL: Anemia and other blood changes in syphilis. JAMA 91:691–700, 1928

    Google Scholar 

  42. Gardner FH, Mettier SR: Lymphocytic leukemoid reaction of the blood associated with miliary tuberculosis. Blood 4:767–775, 1949

    Google Scholar 

  43. Bichel J: Lymphatic leukemia and lymphatic leukemoid states in cancer of the stomach. Blood 4:759–766, 1949

    Google Scholar 

  44. Schlimok G, Thiel E, Rieber EP, Huhn D, Feucht H, Lohmeyer J, Reithmuller: Chronic leukemia with a hybrid surface phenotype (T lymphocytic/myelomonocytic): Leukemic cells displaying natural killer activity and antibody-dependent cellular cytotoxicity. Blood 59:1157–1162, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Allergy and Clinical Immunology, Università della Sapienza, Rome, Italy

    Franco Pandolfi & Fernando Aiuti

  2. Department of Hematology, Università della Sapienza, Rome, Italy

    Franco Mandelli

  3. Department of Clinical Medicine II, Università della Sapienza, Rome, Italy

    Gianpietro Semenzato

  4. Department of Medicine, Università di Padova, Padova, Italy

    Alessandra Ranucci

Authors
  1. Franco Pandolfi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franco Mandelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gianpietro Semenzato
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alessandra Ranucci
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fernando Aiuti
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pandolfi, F., Mandelli, F., Semenzato, G. et al. Classification of patients with T-cell chronic lymphocytic leukemia and expansions of granular lymphocytes: Heterogeneity of Italian cases by a multiparameter analysis. J Clin Immunol 4, 174–184 (1984). https://doi.org/10.1007/BF00914964

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00914964

Key words

Search

Navigation