MicroRNA Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are regulators of gene expression. A role for microRNAs in leukemia, such as chronic lymphoblastic leukemia, acute myelogeneous leukemia has recently been recognized. However, little is known about the role of microRNAs in childhood acute lymphoblastic leukemia (ALL). To determine whether miRNAs are associated with the clinical features of childhood ALL and its association with cytogenetic abnormalities, we analyzed 60 untreated childhood ALL cases for their miRNA expression using a microarray platform. Leukemic samples were collected from the ALL children between 1–18 years of age. Of the 365 miRNA analyzed with a training group of 40 patients, a miRNA signature was derived that was associated with event-free survival. The signature was tested in a validation group of 20 patients. For the latter, a miRNA compound covariate predictor (i.e., a miRNA risk score) was computed on the basis of weighted levels of the miRNAs forming the outcome signature. The signature identified from the training group contained 5 miRNA highly associated with event-free survival (P<0.05). The summary value of the signature miRNA was also highly associated with event-free survival (P <0.05) in the validation group. After adjustment for the gender, age, initial white counts, immunophenotypes, and cytogenetics, the miRNA risk score remained associated with event-free survival (P <0.05) in multivariable analysis. In conclusion, we have identified a miRNA signature of 5 miRNAs which is highly associated with the clinical outcome, cytogenetic and immunophenotypic subtypes of childhood ALL.