Bone marrow cyclooxygenase-2 levels are elevated in chronic-phase chronic myeloid leukaemia and are associated with reduced survival.

Abstract

Increased angiogenesis is important in the pathophysiology of haematological malignancies. Cyclooxygenase-2 (Cox-2) converts arachidonic acid to prostaglandins, which induce expression of angiogenic factors, including vascular endothelial growth factor (VEGF), basic-fibroblast growth factor, transforming growth factor-beta and interleukin 6. Cox-2 may also reduce apoptosis and reduce cellular attachment to the extracellular matrix (ECM). Increased bone marrow (BM) vascularity, increased BM cellular and plasma VEGF levels, and decreased progenitor adherence to BM ECM have all been observed in chronic myeloid leukaemia (CML). We investigated the prognostic significance of levels of Cox-2 in BM cells from patients with CML. Western blot and solid-phase radioimmunoassay (RIA) were used to measure Cox-2 BM levels in 149 patients with chronic phase CML (CP CML). Results were compared with those of normal controls. Expression of Cox-2 was significantly higher in CML than in normal controls (P < 0.0001). Increasing levels of Cox-2 were significantly associated with shorter survival (P = 0.0002, Cox proportional hazard model). A multivariate model based on Cox-2 and degree of splenomegaly was developed for survival in patients with early CP CML. Agents that inhibit Cox-2 activity merit investigation in patients with CP CML.