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

Abstract

Ki-67 is a nuclear antigen that is expressed in all stages of the cell cycle, except G0, 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 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 IgVH mutation status. In a multivariate model incorporating the cKi-67 index with B2M and IgVH, 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

IL-21 and CD40L signals from autologous T cells can induce antigen-independent proliferation of CLL cells

“…42 The circulating Ki-67 index in plasma significantly correlated with lymph node involvement and high values of this index were associated with shorter survival. 43 The recently reported antigenindependent propensity for autonomous BCR signaling might be a crucial contribution to proliferation in CLL.…”

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model

“…The desmin positive cells were also co-stained for Ki67, a marker for proliferation, as denoted by the arrows in Fig. 8 (Bruey et al, 2010;Diniz et al, 2011;Scholzen and Gerdes, 2000). The skeletal muscle matrix recruited significantly more desmin-positive cells when compared to the collagen matrix at 3, 5 and 7 d post-injection, a trend that continued at day 14 (Fig.…”

Telomerase reverse transcriptase catalytic subunit expression and proliferation index in Wilms tumor

“…It is preferentially expressed during late G1, S, M, and G2 phases of the cell cycle. In contrast, cells in the quiescent (G0) phase are negative for this protein [8]. Although the Ki67 protein is well characterized on the molecular level and extensively used as a proliferation marker, its functional significance still remains unclear.…”

“…However, it seems that the expression of Ki67 protein is an absolute requirement for progression through the celldivision cycle [9]. Therefore, Ki67 is accepted as one of the tumor proliferation markers and is an important prognostic indicator in a variety of malignancies especially in prostate and breast carcinomas [8,10].…”