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

Bruey, Jean-Marie; Kantarjian, Hagop; Ma, Wanlong; Estrov, Zeev; Yeh, Chenhsiung; Donahue, Amber; Sanders, Heather; O’Brien, Susan; Keating, Michael; Albitar, Maher

doi:10.1016/j.leukres.2010.03.010

« Previous Next »Leukemia Research
Volume 34, Issue 10 , Pages 1320-1324, October 2010

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

Jean-Marie Bruey
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
Hagop Kantarjian
- Department of Leukemia Department, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Wanlong Ma
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
Zeev Estrov
- Department of Leukemia Department, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Chenhsiung Yeh
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
Amber Donahue
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
Heather Sanders
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
Susan O’Brien
- Department of Leukemia Department, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Michael Keating
- Department of Leukemia Department, MD Anderson Cancer Center, University of Texas, Houston, TX, USA
Maher Albitar
- Department of Hematology and Oncology R&D, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA 92690, USA
- Corresponding author. Tel.: +1 949 728 4784; fax: +1 949 728 7781.

Received 17 November 2009; received in revised form 19 January 2010; accepted 4 March 2010. published online 07 March 2011.

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 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.