Prognostic significance of Tie-1 protein expression in patients with early chronic phase chronic myeloid leukemia.

Abstract

The Tie-1 tyrosine kinase receptor and its thus far unidentified ligand appear to play a distinct role in the regulatory pathways of early hematopoiesis and angiogenesis. Because vascularity is increased in the bone marrow of patients with chronic myeloid leukemia (CML), the authors evaluated the clinical significance of Tie-1 expression in such patients. Using Western blot analysis and solid-phase radioimmunoassay (RIA), the authors quantified Tie-1 protein in bone marrow samples from 128 patients with CML and 31 normal controls. The median Tie-1 RIA value of CML samples was significantly higher than in normal controls (P = 0.01). The authors found no significant differences in Tie-1 levels in patients with early chronic, late chronic, accelerated, and blastic phases (P = 0.2). High Tie-1 levels correlated with short survival in patients with early chronic phase (P = 0.003; Cox proportional hazard model) but not in patients with late chronic (P = 0.2) or accelerated/blastic (P = 0.2) phase CML. Tie-1 protein level was also prognostic when patients were separated into two groups by the median value. High Tie-1 level in early chronic phase was associated with significantly shorter survival than low Tie-1 level (median survival, 116 vs. 61 months; P = 0.03). In patients with early chronic phase CML, Tie-1 levels correlated directly with patient age (P = 0.004) and platelet count (P = 0.003), and inversely with leukocyte count (P = 0.007). Tie-1 as a predictor of survival in early chronic phase CML was independent of risk group, spleen size, age, hemoglobin, and basophil count (P = 0.03; multivariate Cox proportional hazard model). The authors' findings support the hypothesis that angiogenesis may play a major role in the pathophysiology of chronic phase CML.