title: Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia.
abstract: A genome-wide serum miRNA expression analysis previously showed the upregulation of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with healthy controls. The aim of this study was to investigate the expression patterns and the prognostic relevance of miR-375 in pediatric AML. Expression levels of miR-375 in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. Expression levels of miR-375 in the bone marrow of pediatric AML patients were significantly higher than those in normal controls (P < 0.001). Then, miR-375 upregulation occurred more frequently in French-American-British classification subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the expression levels of miR-375 in pediatric AML patients with unfavorable karyotypes were dramatically higher than those in intermediate and favorable groups (P = 0.002). Moreover, high miR-375 expression was significantly associated with shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001) in pediatric AML patients. Multivariate analysis further identified miR-375 expression and cytogenetics risk as independent prognostic factors for both relapse-free survival and overall survival. In particular, the prognostic relevance of miR-375 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our findings suggest for the first time that the upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric AML. Since its correlation with poor relapse-free survival and overall survival, miR-375 may be a novel biomarker to improve the management of pediatric AML patients.
authors.affiliation: Department of Pediatrics, Huai'an Hospital Affiliated of Xuzhou Medical College and Huai'an Second People's Hospital, 62 Huaihai Road South, Huai'an, 223002, P. R. China.
authors.forename: Zhengyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Ze
authors.initials: Z
authors.lastname: Hong
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Weijing
authors.initials: W
authors.lastname: Feng
mesh_terms: D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015999:Multivariate Analysis; D011379:Prognosis; D016896:Treatment Outcome; D015854:Up-Regulation / Q000235:genetics*
chemical_list: C540933:MIRN375 microRNA, human; D035683:MicroRNAs