NDRG1 EXPRESSION IN CHILDHOOD LEUKEMIA AND ITS CORRELATION TO PROGNOSIS AND THERAPEUTIC RESPONSE

Abstract

INTRODUCTION: N-myc downstream regulated gene 1 (NDRG1) gene expression has been found to be downregulated in a variety of solid tumors and is now regarded as a suppressor gene. However, little is known about its possible role in hematologic cancers. OBJECTIVE: Our goal was to study expression of the NDRG1 gene in childhood leukemia and explore a possible correlation between expression and prognostic factors. METHODS: Bone marrow or peripheral blood mononuclear cells from 65 children with leukemia and peripheral blood mononuclear cells from 12 healthy control children were isolated: NDRG1 messenger RNA expression was determined by fluorescence real-time polymerase chain reaction. RESULTS: NDRG1 messenger RNA expression in acute leukemia groups collectively (acute lymphocytic leukemia [ALL] [41 cases] and acute monocytic leukemia [24 cases]) was significantly lower than that of normal controls (normalized ratios of NDRG1 to glyceraldehyde-3-phosphate dehydrogenase copy numbers were 0.27 and 0.25 vs 0.30 and 0.86 in controls, respectively; P < .01), although there was no statistically significant difference between the ALL and acute monocytic leukemia groups. NDRG1 expression was significantly lower in prednisone nonresponder ALL (13 cases) than in prednisone good-responder ALL (15 cases) (normalized ratios: 0.13 and 0.38, respectively). Similarly, NDRG1 expression was significantly downregulated in high-risk ALL (17 cases) than that in lower-risk ALL (24 cases) (normalized ratios: 0.15 and 0.30, respectively). CONCLUSIONS: NDRG1 expression was remarkably downregulated in childhood leukemia, as in other human solid tumors. In addition, its expression in childhood ALL was closely associated with such prognostic factors as prednisone response and risk stratification. Our research suggests that NDRG1 expression is negatively correlated to ALL prognosis and therapeutic response.