miRNAs in Lymphocytic Leukaemias—The miRror of Drug Resistance

Abstract

Refractory disease and relapse remain the main causes of cancer therapy failure. Refined risk stratification, treatment regimens and improved early diagnosis and detection of minimal residual disease have increased cure rates in malignancies like childhood acute lymphoblastic leukaemia (ALL) to 90%. Nevertheless, overall survival in the context of drug resistance remains poor. The regulatory role of micro RNAs (miRNAs) in cell differentiation, homeostasis and tumorigenesis has been under extensive investigation in different cancers. There is accumulating data demonstrating the significance of miRNAs for therapy outcomes in lymphoid malignancies and some direct demonstrations of the interplay between these small molecules and drug response. Here, we summarise miRNAs’ impact on chemotherapy resistance in adult and paediatric ALL and chronic lymphocytic leukaemia (CLL). The main focus of this review is on the modulation of particular signaling pathways like PI3K-AKT, transcription factors such as NF-κB, and apoptotic mediators, all of which are bona fide and pivotal elements orchestrating the survival of malignant lymphocytic cells. Finally, we discuss the attractive strategy of using mimics, antimiRs and other molecular approaches pointing at miRNAs as promising therapeutic targets. Such novel strategies to circumvent ALL and CLL resistance networks may potentially improve patients’ responses and survival rates.