Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease activity.
Ki-67 is a monoclonal antibody that recognises a nuclear antigen expressed during most phases of the cell cycle. We have analysed, by immunocytochemistry, the frequency, morphology, and clinical significance of Ki-67+ cells in 108 patients with B-cell chronic lymphocytic leukemia (CLL). Because in normal peripheral blood Ki-67+ cells are mainly T lymphocytes, we have also investigated, by double immunoenzymatic staining, the proportion of Ki-67+ T cells (Ki-67/CD3+) in CLL. Four groups of patients were identified: (i) 47 with stage A, (ii) 32 with stages B + C, (iii) 24 with greater than 10% of circulating prolymphocytes (CLL/PL) and (iv) five with Richter's syndrome. Within stage A CLL, two groups were considered: A' (Hb greater than or equal to 12 g/dl and lymphocytes less than 30 + 10(9)/l) and A" (Hb less than 12 g/dl or lymphocytes greater than or equal to 30 x 10(9)/l). The percentage and absolute number of Ki-67+ leukemic cells was found to increase with the stage of the disease and correlate with the proportion of prolymphocytes. On the other hand, the proportion of Ki-67+ T cells (CD3+) was significantly higher in patients with CLL stage A' (29.3 +/- 4.5), which includes patients with long-standing, stable disease, than in CLL stage A" (9.5 +/- 3.3), B + C (7.1 +/- 4.6), and CLL/PL (6.4 +/- 2.8). Ki-67 seems to identify patients with more aggressive forms of CLL, such as CLL/mu 2PL with more than 10% Ki-67+ cells (25% of the cases) and Richter's syndrome, in which all the large lymphoma cells are Ki-67+. Long-term follow-up will establish whether Ki-67 is a good prognostic marker and can predict disease outcome.
Cordone
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Academic Department of Hematology and Cytogenetics, Royal Marsden Hospital, London, UK.
Matutes
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E
Catovsky
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D
D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D017252:CD3 Complex; D002453:Cell Cycle; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000276:immunology / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell