The Role of MicroRNA in Paediatric Acute Lymphoblastic Leukaemia: Challenges for Diagnosis and Therapy.

Carle Grobbelaar,Anthony M Ford

doi:10.1155/2019/8941471

Abstract

Acute lymphoblastic leukaemia (ALL) is the most common cancer of childhood. Although the overall survival of children with ALL is now more than 90%, leukaemia remains one of the leading causes of death from disease. In developed countries, the overall survival of patients with ALL has increased to more than 80%; however, those children cured from ALL still show a significant risk of short- and long-term complications as a consequence of their treatment. Accordingly, there is a need not only to develop new methods of diagnosis and prognosis but also to provide patients with less toxic therapies. MicroRNAs (miRNAs) are small ribonucleic acids (RNA), usually without coding potential, that regulate gene expression by directing their target messenger RNAs (mRNAs) for degradation or translational suppression. In paediatric ALL, several miRNAs have been observed to be overexpressed or underexpressed in patient cohorts compared to healthy individuals, while numerous studies have identified specific miRNAs that can be used as biomarkers to diagnose ALL, classify it into subgroups, and predict prognosis. Likewise, a variety of miRNAs identify as candidate targets for treatment, although there are numerous obstacles to overcome before their clinical use in patients. Here, we summarise the roles played by different miRNAs in childhood leukaemia, focussing primarily on their use as diagnostic tools and potential therapeutic targets, as well as a role in predicting treatment outcome. Finally, we discuss the potential roles of miRNA in immunotherapy and the novel contributions made by gut miRNAs to regulation of the host microbiome.

Highlights

Leukaemia, the most common paediatric cancer, accounts for approximately one-third of malignancies diagnosed in children below 16 years of age [1]
MiRNAs are differentially expressed in distinct stages of lymphopoiesis and influence the maturation process of lymphoid precursors. e aberrant miRNA signatures observed in acute lymphoblastic leukaemia (ALL) can be used to define biomarkers for diagnosis, classification, and prognosis of this disease
Circulating miRNAs can be detected with the use of sensitive and applicable methods such as RT-qPCR, allowing for easy detection and a minimally invasive approach for diagnosis of ALL

Summary

Introduction

The most common paediatric cancer, accounts for approximately one-third of malignancies diagnosed in children below 16 years of age [1]. Rough treatment stratification by immunophenotype and genotype, the incorporation of more effective drug combinations into treatment protocols, and improved supportive care, overall survival of patients with ALL has increased to more than 80% in developed countries [3,4,5]. Despite the dramatically improved survival rates achieved with most treatment protocols, leukaemia in children remains one of the leading causes of death from disease. There is a need for the development of new therapies to effectively treat children with high-risk disease, as well as a better optimization of current treatment strategies for low-risk disease

MicroRNA Biology and the Role in Cancer

Future Perspectives

Findings

Conclusions