Prognostic significance of cathepsin L expression in pediatric acute myeloid leukemia.

Abstract

Overexpression of cathepsin L (CTSL), an endolysosomal cysteine protease, is associated with inferior survival of patients with various human malignancies. We evaluated the expression/activity of CTSL in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMMCs) of 103 pediatric acute myeloid leukemia (AML) patients to assess its prognostic significance in this malignancy. Thirty-five healthy siblings of patients served as controls. Our results revealed significantly higher CTSL activity (p < .0001), protein (p < .05), and mRNA levels (p < .01) in both PBMCs and BMMCs of patients as compared with controls. BMMCs displayed higher activity of CTSL than PBMCs (p < .01). A dramatic reduction in CTSL activity was recorded after chemotherapy in a significant proportion (74%) of patients (p < .0001). By multivariate analysis, CTSL in BMMCs emerged as a strong independent prognostic marker for overall survival (OS) (p = .004). Thus, our results suggest the potential utility of CTSL in predicting the outcome of pediatric AML.