title: MicroRNA-223 expression is uniformly down-regulated in B cell lymphoproliferative disorders and is associated with poor survival in patients with chronic lymphocytic leukemia.
abstract: MicroRNA-223 (miR-223) expression has been demonstrated to be stage-specific in B cell differentiation and associated with the outcome of chronic lymphocytic leukemia (CLL). However, the expression pattern of miR-223 in B cell lymphoproliferative disorders and its association with the outcome of Chinese patients with CLL have not been investigated. In this study, we demonstrated that miR-223 expression was significantly decreased in CLL, mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL). In CLL, miR-223 expression decreased significantly with progression from early to advanced clinical stages and was significantly lower in patients with elevated β(2)-microglobulin, unmutated immunoglobulin variable heavy chain (IgVH) gene or with disease progression or death. Using a cut-off determined by receiver operating characteristic (ROC) analysis optimizing concordance with IgVH mutational status, miR-223-negative and -positive groups were defined for 22 and 31 patients, respectively. The median progression-free survival (PFS) and overall survival of the miR-223-negative group were 13 and 40 months, respectively, significantly shorter than for the miR-223-positive group (both not reached; p = 0.002 and p = 0.018, respectively). Multivariate analysis revealed that the absence of miR-223 was the only independent factor capable of predicting shorter PFS. In conclusion, miR-223 is uniformly down-regulated in B-LPDs and is a useful prognostic factor for patients with CLL.
authors.affiliation: Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences, Tianjin, China.
authors.forename: Keshu
authors.initials: K
authors.lastname: Zhou
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yi
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Li
authors.forename: Yanying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dehui
authors.initials: D
authors.lastname: Zou
authors.forename: Junyuan
authors.initials: J
authors.lastname: Qi
authors.forename: Yaozhong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lugui
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001402:B-Lymphocytes / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; C525067:MIR223, human