title: 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 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.
authors.affiliation: Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Bruey
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Wanlong
authors.initials: W
authors.lastname: Ma
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.forename: Chenhsiung
authors.initials: C
authors.lastname: Yeh
authors.forename: Amber
authors.initials: A
authors.lastname: Donahue
authors.forename: Heather
authors.initials: H
authors.lastname: Sanders
authors.forename: Susan
authors.initials: S
authors.lastname: O'Brien
authors.forename: Michael
authors.initials: M
authors.lastname: Keating
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D019394:Ki-67 Antigen / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D001613:beta 2-Microglobulin / Q000097:blood
chemical_list: D015415:Biomarkers; D019394:Ki-67 Antigen; D001613:beta 2-Microglobulin