Deoxycytidine kinase and cN‐II nucleotidase expression in blast cells predict survival in acute myeloid leukaemia patients treated with cytarabine

Abstract

Summary. The cytotoxic activity of cytarabine (ara‐C) in leukaemic blasts depends on activating enzymes such as deoxycytidine kinase (dCK) and inactivating enzymes such as the 5′‐nucleotidases. We have analysed dCK and ‘high‐Km’ 5′‐nucleotidase (cN‐II) mRNA expression by the quantitative real‐time polymerase chain reaction at diagnosis in leukaemic blasts from 115 acute myeloid leukaemia (AML) patients treated with ara‐C. The prognostic value of these parameters as well as that of the cN‐II/dCK ratio was determined. In univariate analyses: (1) low levels of dCK, high levels of cN‐II and a high cN‐II/dCK ratio predicted shorter disease‐free survival (DFS); (2) low levels of dCK and cN‐II/dCK ratio also predicted shorter overall survival (OS). In a multivariate analysis taking into account other clinical and laboratory variables: (1) high cN‐II expression, a high cN‐II/dCK ratio, age ≥ 60 years and an unfavourable karyotype were independent prognostic factors for DFS; and (2) a high cN‐II/dCK ratio, age ≥ 60 years and an unfavourable karyotype predicted shorter OS. Age, karyotype and cN‐II/dCK ratio were used to define a prognostic score that permitted the identification of high‐ and low‐risk groups. Our results suggest that dCK and cN‐II mRNA expression in leukaemic blasts at diagnosis is correlated with clinical outcome and may play a functional role in the resistance to ara‐C in patients with AML.