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Circulating Ki-67 index in plasma as a biomarker and prognostic indicator in chronic lymphocytic leukemia

2010; Elsevier BV; Volume: 34; Issue: 10 Linguagem: Inglês

10.1016/j.leukres.2010.03.010

1873-5835

Jean-Marie Bruey, Hagop M. Kantarjian, Wanlong Ma, Zeev Estrov, Chen-Hsiung Yeh, Amber C. Donahue, Heather Sanders, Susan O’Brien, Michael J. Keating, Maher Albitar,

Neuroendocrine Tumor Research Advances

Ki-67 is a nuclear antigen that is expressed in all stages of the cell cycle, except G(0), and is widely used as a marker of cellular proliferation in human tumors. We recently showed that elevated levels of Ki-67 circulating in plasma (cKi-67) are associated with shorter survival in patients with acute lymphoblastic leukemia. The current study included 194 patients with CLL and 96 healthy control subjects. cKi-67 levels in plasma were determined using an electrochemiluminescent immunoassay. We normalized the cKi-67 level to the absolute number of lymphocytes in the patient's peripheral blood to establish the plasma cKi-67 index. The cKi-67 index showed significant correlation with lymph node involvement and Rai stage (P=0.05). Higher cKi-67 index values were significantly associated with shorter survival. Multivariate Cox proportional hazards regression analysis demonstrated that the association of the cKi-67 index with shorter survival was independent of IgV(H) mutation status. In a multivariate model incorporating the cKi-67 index with B2M and IgV(H), only cKi-67 index and B2M levels remained as independent predictors of survival. The results of this study suggest that the plasma cKi-67 index, along with B2M level, is a strong predictor of clinical behavior in CLL.