MICRORNA EXPRESSION PROFILING OF BONE MARROW AND PERIPHERAL BLOOD SAMPLES IN CHILDREN WITH B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: MIRNAS AS POTENTIAL BIOMARKERS

Abstract

Objectives: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease characterized by altered clonal proliferation of lymphoid progenitor cells and their accumulation in the bone marrow (BM) and other organs. Precursor B-cell ALL (B-ALL) is the most common immunological subtype of ALL and the most frequent cancer in children. According to the World Health Organization, any disease classification must be periodically reviewed and updated, thus, there is a constant need for the characterization of new molecular biomarkers for diagnostic and prognostic purposes. This study aimed to compare microRNA (miRNA) expression profiles between bone marrow and peripheral blood samples and evaluate potential diagnostic biomarkers for childhood B-ALL. Materials and methods: Peripheral blood and bone marrow samples were collected from children with B-ALL admitted to the Onco-Hematology Service of the Joana de Gusmão Children's Hospital (HIJG), Florianópolis, Santa Catarina, as well as healthy controls. The samples were subjected to miRNA microarray analysis followed by RT-qPCR validation. Results: Microarray analysis revealed no differences in miRNA expression between peripheral blood and bone marrow samples from the same B-ALL patients. Comparison of peripheral blood profiles between B-ALL and control subjects revealed 13 differentially expressed miRNAs, and among these, five were selected as potential biomarkers for RT-qPCR validation based on their respective expression status. Additionally, nine miRNAs were included in the RT-qPCR validation based on literature findings. RT-qPCR analysis did not show significant differences between bone marrow and peripheral blood samples for 12 of the 14 miRNAs tested. Furthermore, it was found that one miRNA was downregulated and 10 were upregulated in B-ALL patients. Enriched pathway analysis of these differentially expressed miRNAs identified genes with important regulatory roles associated with cell cycle, proliferation, and apoptosis. Discussion: miRNA profile signatures have a high potential for cancer diagnosis, including that of childhood acute leukemia. In this study, we demonstrate important similarities between miRNA profile signatures of peripheral blood and bone marrow samples of children with B-ALL. Also, we demonstrated that some miRNAs are differentially expressed in leukemia patients when compared with healthy controls. Importantly, receiver operating characteristic analysis showed that all miRNAs significantly altered in B-ALL had high performance and could be used to distinguish patients from healthy subjects. Conclusion: Together, these data suggest an equivalence between peripheral blood and bone marrow miRNA expression profiles and demonstrate the potential of some miRNAs as B-ALL biomarkers.