High serum concentration of YKL-40 is associated with short survival in patients with acute myeloid leukemia

Abstract

Purpose: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth or differentiation factor, play a role in angiogenesis, or protect against apoptosis. High serum YKL-40 is associated with poor prognosis in solid carcinomas. The aim was to examine serum YKL-40 in patients with acute myeloid leukemia (AML).

Experimental design: YKL-40 was measured by ELISA in serum from 77 patients recently diagnosed with AML before and during the first month of chemotherapy.

Results: Forty (52%) of the AML patients had elevated serum YKL-40 (compared with age-matched healthy subjects) and their survival was shorter than in patients with normal serum YKL-40 (median, 128 days; interquartile range, 18-629 days versus 386 days; interquartile range, 180-901; P=0.018 Mann-Whitney test). Univariate analysis of serum YKL-40 (logarithmically transformed and treated as a continuous covariate) showed significant association with survival within the first month after start of chemotherapy [hazard ratio (HR), 1.7; 95% confidence interval (CI), 1.2-2.4; P=0.002], first 12 months (HR, 1.6; 95% CI, 1.2-2.0; P=0.0002), and overall survival (HR, 1.3; 95% CI, 1.1-1.6; P=0.003). Multivariate Cox analysis showed that serum YKL-40 was an independent prognostic variable for survival (first month: HR, 1.7; P=0.011; 12 months: HR, 1.6; P=0.0002; overall survival: HR, 1.4; P=0.002). High serum YKL-40 at start of chemotherapy was a risk factor for pneumonia within the first month, and serum YKL-40 increased (P=0.002) at time of pneumonia and was unchanged in patients without infections.

Conclusions: Serum YKL-40 is a prognostic biomarker of survival in AML patients. Its role in AML and infections needs to be determined.