High serum microRNA-335 level predicts aggressive tumor progression and unfavorable prognosis in pediatric acute myeloid leukemia.

Abstract

MiRNA expression profiles previously showed the higher expression of microRNA(miR)-335 in bone marrow samples of pediatric acute myeloid leukemia (AML) patients than normal controls. Our aim was to investigate associations of miR-335 expression with tumor progression and prognosis in pediatric AML. Real-time quantitative PCR was performed to detect the expression of miR-335 in bone marrow mononuclear cells and serum obtained from patients with pediatric AML and healthy controls. Expression levels of miR-335 in the bone marrow and serum of pediatric AML patients were both significantly higher than those in normal controls (both P < 0.001). Then, high serum miR-335 level occurred more frequently in French-American-British classification subtype M7 subtype than in other subtypes (P = 0.03). The expression of serum miR-335 in pediatric AML patients with unfavorable karyotypes was also significantly higher than those in intermediate and favorable groups (P = 0.008). Moreover, high serum miR-335 level was markedly associated with shorter relapse-free and overall survivals (both P < 0.001) of patients with pediatric AML. Furthermore, the multivariate analysis identified the serum miR-335 and cytogenetics risk as independent prognostic factors for both relapse-free and overall survivals. More importantly, the prognostic relevance of serum miR-335 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our data offer the convincing evidence for the first time that serum miR-335 level may be markedly and consistently increased in pediatric AML patients. Serum miR-335 may serve as a promising marker for monitoring the progression and predicting the clinical outcome of patients with this disease.