Circulating Ki67 positive lymphocytes in multiple myeloma and benign monoclonal gammopathy.

AIMS--To estimate the proportion and nature of the proliferating (Ki67+) circulating lymphocytes in a series of patients with multiple myeloma and monoclonal gammopathy of unknown significance (MGUS) and to correlate this with other clinical and laboratory parameters, using blood from healthy adults as a control. To investigate the extent to which the B and T lymphoid components are involved in progression and/or control of disease. METHODS--Blood lymphocytes from 15 patients with multiple myeloma, 10 patients with MGUS and 10 healthy adults were analysed using a sequential double immunoenzymatic staining technique. Antibodies directed against Ki67 were used to detect cells in cycle, CD3, CD4, and CD8 to identify T cells, HLA-Dr as a marker for B cells and activated T cells, and CD11b as a marker for natural killer cells. Polyclonal antibodies directed against the kappa and lambda immunoglobulin light chains were also used to detect B cells. RESULTS--The proportion of proliferating (Ki67+) lymphocytes was significantly higher in patients with multiple myeloma (6.8 +/- 2.6) and MGUS (3.5 +/- 1.1) compared with the normal controls (1.69 +/- 0.3); this was also true when multiple myeloma and MGUS cases were compared. In multiple myeloma and MGUS over 50% of the Ki67+ cells were activated T lymphocytes (CD3+/HLA-Dr+); a minority (11%) were non-clonal B lymphocytes. In contrast to controls (6.7 +/- 1.9), in patients with multiple myeloma and MGUS the proportion of proliferating T cells expressing CD8 (23.6 +/- 12.5 and 15.3 +/- 7.7, respectively) and CD11b (13 +/- 8.7 and 11.6 +/- 3.9, respectively) was higher. In multiple myeloma there was a positive correlation between the proportion of Ki67+ lymphocytes, beta-2-microglobulin concentrations and disease stage. CONCLUSIONS--Although the number of patients investigated is small, this study suggests that Ki67 expression in blood lymphocytes from patients with multiple myeloma may be a good prognostic indicator for aggressive disease and may help to distinguish multiple myeloma from MGUS. The activated proliferating T cells in these diseases may represent an immunological reaction against the tumour.

[1]  W. O'Fallon,et al.  Plasma cell labeling index and β2-microglobulin predict survival independent of thymidine kinase and C-reactive protein in multiple myeloma , 1993 .

[2]  P. Sonneveld,et al.  Analysis of multidrug‐resistance (MDR‐1) glycoprotein and CD56 expression to separate monoclonal gammopathy from multiple myeloma , 1993, British journal of haematology.

[3]  D. Catovsky,et al.  Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease activity. , 1992, Leukemia.

[4]  R. Kyle,et al.  Diagnostic criteria of multiple myeloma. , 1992, Hematology/oncology clinics of North America.

[5]  J. Miguel,et al.  Lymphoid subsets and prognostic factors in multiple myeloma , 1992, British journal of haematology.

[6]  D. Catovsky,et al.  Characterisation of normal peripheral blood cells in cycle identified by monoclonal antibody Ki-67. , 1992, Journal of clinical pathology.

[7]  A. Órfão,et al.  Increased expression of natural‐killer‐associated and activation antigens in multiple myeloma , 1992, American journal of hematology.

[8]  B. Barlogie,et al.  New treatment strategies for multiple myeloma , 1990, American journal of hematology.

[9]  R. Casale,et al.  Multiple myeloma: Relationship between survival and cellular morphology , 1990, American journal of hematology.

[10]  J. S. San Miguel,et al.  Prognostic factors and classification in multiple myeloma. , 1989, British Journal of Cancer.

[11]  J. Gerdes,et al.  Determination of the growth fraction in monoclonal gammopathy with the monoclonal antibody Ki‐67 , 1988, British journal of haematology.

[12]  W. O'Fallon,et al.  Value of beta 2-microglobulin level and plasma cell labeling indices as prognostic factors in patients with newly diagnosed myeloma. , 1988, Blood.

[13]  T. Grogan,et al.  Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67 , 1988 .

[14]  D. Joshua.  Biology of multiple myeloma—host‐tumour interactions and immune regulation of disease activity , 1988, Hematological oncology.

[15]  T. Lister,et al.  The prognostic value of Ki67 immunostaining in non‐Hodgkin's lymphoma , 1988, The Journal of pathology.

[16]  T. Grogan,et al.  Independent prognostic significance of a nuclear proliferation antigen in diffuse large cell lymphomas as determined by the monoclonal antibody Ki-67. , 1988, Blood.

[17]  S. Linn,et al.  Prognostic significance of plasma cell morphology in multiple myeloma , 1987, Cancer.

[18]  B. Durie.  Staging and kinetics of multiple myeloma. , 1982, Seminars in oncology.

[19]  F. Mandelli,et al.  Low plasma cell 3(H) thymidine incorporation in monoclonal gammopathy of undetermined significance (MGUS), smouldering myeloma and remission phase myeloma: a reliable indicator of patients not requiring therapy , 1984, British journal of haematology.

[20]  R. Foà,et al.  Membrane phenotype and functional behaviour of T lymphocytes in multiple myeloma: correlation with clinical stages of the disease. , 1984, Clinical and experimental immunology.

[21]  Johannes Gerdes,et al.  Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation , 1983, International journal of cancer.

[22]  F. Mandelli,et al.  Smouldering multiple myeloma. , 1981, Haematologica.

[23]  R. Kyle,et al.  Smoldering multiple myeloma. , 1980, The New England journal of medicine.

[24]  R. Alexanian,et al.  Clinical classification of plasma cell myeloma. , 1975, Archives of internal medicine.

[25]  Proposed guidelines for protocol studies. II. Plasma cell myeloma. Prepared by a Committee of the Chronic Leukemia--Myeloma Task Force, National Cancer Institute. , 1968, Cancer chemotherapy reports. Part 3.