MicroRNA patterns associated with clinical prognostic parameters and CNS relapse prediction in pediatric acute leukemia.
BACKGROUND
Recent reports have indicated that microRNAs (miRNAs) play a critical role in malignancies, and regulations in the progress of adult leukemia. The role of miRNAs in pediatric leukemia still needs to be established. The purpose of this study was to investigate the aberrantly expressed miRNAs in pediatric acute leukemia and demonstrate miRNA patterns that are pediatric-specific and prognostic parameter-associated.


RESULTS
A total of 111 pediatric bone marrow samples, including 99 patients and 12 normal donors, were enrolled in this study. Of those samples, 36 patients and 7 normal samples were used as a test cohort for the evaluation of miRNA profiling; 63 pediatric patients and 5 normal donors were used as a validation cohort to confirm the miRNA differential expression. Pediatric ALL- and AML-specific microRNA expression patterns were identified in this study. The most highly expressed miRNAs in pediatric ALL were miR-34a, miR-128a, miR-128b, and miR-146a, while the highly expressed miRNAs in pediatric AML were miR-100, miR-125b, miR-335, miR-146a, and miR-99a, which are significantly different from those reported for adult CLL and AML. miR-125b and miR-126 may serve as favorable prognosticators for M3 and M2 patients, respectively. Importantly, we identified a "miRNA cascade" associated with central nervous system (CNS) relapse in ALL. Additionally, miRNA patterns associated with prednisone response, specific risk group, and relapse of ALL were also identified.


CONCLUSIONS
There are existing pediatric-associated and prognostic parameter-associated miRNAs that are independent of cell lineage and could provide therapeutic direction for individual risk-adapted therapy for pediatric leukemia patients.
Zhang
Hua
H
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, Sun Yat-Sen University, Guangzhou, PR China.
Luo
Xue-Qun
XQ
Zhang
Peng
P
Huang
Li-Bin
LB
Zheng
Yu-Sheng
YS
Wu
Jun
J
Zhou
Hui
H
Qu
Liang-Hu
LH
Xu
Ling
L
Chen
Yue-Qin
YQ
D016543:Central Nervous System Neoplasms / Q000175:diagnosis* / Q000209:etiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk
D035683:MicroRNAs