[Expression of microRNA-223 and its clinical value in B lymphoproliferative disorders].
OBJECTIVE
To detect the expression of microRNA-223 and analyze its clinical value in B lymphoproliferative disorders.


METHODS
Peripheral blood samples (n = 78) and bone marrow samples (n = 9) were collected from patients with chronic lymphocytic leukemia (CLL, n = 53), mantle cell lymphoma (MCL, n = 13), splenic marginal zone lymphoma (SMZL, n = 9) and healthy donors (n = 12) at our hospital from 2003 to 2010. Mononuclear cells were isolated and B cells purified with a CD19(+) magnetic-bead system. Total RNA was extracted from purified CD19(+) cells and the expression of microRNA-223 measured by TaqMan microRNA quantitative polymerase chain reaction (PCR). The clinical data of these patients were collected and their outcomes analyzed with SPSS 16.0 software.


RESULTS
(1) The levels of microRNA-223 in CLL, MCL and SMZL were 4.58 ± 0.62, 4.03 ± 0.54 and 4.63 ± 0.57 respectively. And they were significantly lower than that in normal B cells (5.69 ± 0.60, P < 0.01). The expression of microRNA-223 decreased significantly in MCL versus CLL and SMZL (P < 0.05). There was no statistical difference between CLL and SMZL (P > 0.05). (2) The down-regulation of microRNA-223 was associated with disease aggressiveness in CLL. Patients with unmutated immunoglobulin heavy chain variable region (IgVH) expressed significantly a lower level of microRNA-223 (4.05 ± 0.69 vs 4.67 ± 0.51, P = 0.003). In 13q-negative patients, the expression of microRNA-223 decreased more significantly than that in 13q-positive patients (4.25 ± 0.67 vs 4.76 ± 0.45, P = 0.044). (3) Using receiver operating characteristic (ROC) curve analysis, the microRNA-223 cutoffs were defined according to the IgVH mutational status. The patients were divided into the positive and negative subgroups. The median progression-free survival (PFS) of microRNA-223 positive patient subgroup was 48 months. It was significantly longer than the negative subgroup (P = 0.001). In the microRNA-223 positive subgroup, no patient died at the end of follow-up.


CONCLUSIONS
MicroRNA-223 may play an important role in the pathogenesis of B lymphoproliferative disorders. The down-regulation of microRNA-223 is associated with disease aggressiveness and poor prognostic factors in CLL. It may become a new reliable prognostic predictor.
Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC,State Key Laboratory of Experimental Hematology, Tianjin 300020, China.
Ke-Shu
KS
Zhou
Zhen
Z
Yu
Shu-Hua
SH
Yi
Zeng-Jun
ZJ
Li
Gang
G
An
Yan-Ying
YY
Wang
De-Hui
DH
Zou
Jun-Yuan
JY
Qi
Yao-Zhong
YZ
Zhao
Yong-Ping
YP
Song
Lu-Gui
LG
Qiu
D001402:B-Lymphocytes / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis; D008232:Lymphoproliferative Disorders; D035683:MicroRNAs / Q000235:genetics
D007135:Immunoglobulin Variable Region; D035683:MicroRNAs