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Published on: July 20, 2016
Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease
I Cordone1, E Matutes, D Catovsky
1Academic Department of Hematology and Cytogenetics, Royal Marsden Hospital, London, UK.
Insights
Ki-67 protein levels in leukemia cells increase with disease stage in chronic lymphocytic leukemia (CLL). High Ki-67 T cell proportions may indicate stable disease, suggesting Ki-67
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Ki-67 is a nuclear antigen marker for cell proliferation, expressed throughout the cell cycle.
- Chronic lymphocytic leukemia (CLL) is a heterogeneous B-cell malignancy with varying clinical courses.
- Understanding proliferation markers like Ki-67 is crucial for assessing CLL aggressiveness and prognosis.
Purpose of the Study:
- To analyze the frequency, morphology, and clinical significance of Ki-67 positive (Ki-67+) cells in B-cell chronic lymphocytic leukemia (CLL).
- To investigate the proportion of Ki-67+ T cells in CLL patients.
- To determine if Ki-67 expression can serve as a prognostic marker in CLL.
Main Methods:
- Immunocytochemistry was used to analyze Ki-67+ cells in 108 CLL patients.
- Double immunoenzymatic staining was employed to determine the proportion of Ki-67+ T cells (Ki-67/CD3+).
- Patients were categorized into four groups based on disease stage, prolymphocyte count, and Richter's syndrome.
Main Results:
- The percentage and absolute number of Ki-67+ leukemic cells increased with CLL disease stage and correlated with prolymphocyte proportion.
- The proportion of Ki-67+ T cells was significantly higher in early-stage CLL (Stage A') compared to advanced stages (A", B+C) and CLL/prolymphocytic leukemia (CLL/PL).
- High Ki-67 expression was observed in aggressive forms of CLL, including CLL/PL and Richter's syndrome.
Conclusions:
- Ki-67 expression in leukemic cells correlates with CLL disease progression and prolymphocyte levels.
- A higher proportion of Ki-67+ T cells may be associated with stable, early-stage CLL.
- Ki-67 appears to identify more aggressive CLL subtypes and warrants further investigation as a prognostic marker.
Abstract:
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.

