Abstract 1576: Identification of six novel candidate miRNAs associated with early relapse in B-cell pediatric acute lymphoblastic leukemia
Authors: Amankwah Ernest K. , Maloney Kelly W. , Larsen Eric C. , Devidas Meenakshi , Teachey David T. , Rabin Karen R. , Loh Mignon L. , Brown Patrick A. 
Published: August 2019

Background: Aberrantly expressed miRNAs may contribute to treatment resistance in pediatric acute lymphoblastic leukemia relapse (ALL) and could serve as biomarkers for risk of relapse. However, few studies have evaluated the role of miRNAs in ALL relapse and a consensus clinically significant miRNA signature is yet to be identified. In this study, we identified miRNAs associated with pediatric B-ALL relapse, by profiling ~2,500 miRNAs in two independent sample sets.

Methods: We performed global miRNA profiling using Affymetrix miRNA v 4.0 on two independent samples. Profiling was initially performed on diagnostic bone marrow specimens from 6 early relapse (≤3 years after diagnosis) and 6 age and cytogenetics matched prolonged remission (≥4 years) patients treated at the Johns Hopkins School of Medicine (first set). We then performed profiling on 14 early relapse and 14 matched prolonged remission specimens from patients treated on the Children’s Oncology Group trials AALL0331 and AALL0232 (second set). Global miRNA expression was compared between early relapse and remission samples in each set. Differential expression was determined based on fold change (&gt;1) and false discovery rate q-value (&lt;0.05).

Results: Twelve and 39 top differentially expressed miRNAs were observed in the first (fold change=1.48-4.45, q&lt;0.05) and second (fold change=1.12-2.19, q&lt;0.05) sets, respectively. None of the top differentially expressed miRNAs in the two datasets overlapped. However, six miRNAs (miR-101-3p, miR-4774-5p, miR-1324, miR-631, miR-4699-5p and miR-922) were consistently upregulated in early relapse compared to remission specimens in both the first (fold change=1.13-2.19, q&lt;0.38) and second (fold change=1.48-4.78, all q&lt;0.05) sets; albeit these miRNAs did not meet the q-value threshold in the first set. Four (miR-631, mir-101-3p, miR-922 and miR-1324) out of the six overlapping miRNAs have been previously implicated in key functional oncogenic pathways in adult cancers, including multiple myeloma, prostate, lung, liver, breast and head and neck cancers.

Conclusion: This study provides evidence for a set of six miRNAs that are associated with early relapse in pediatric B-ALL. Although some of the differentially expressed miRNAs have been implicated in adult cancers, none of them have been previously implicated in pediatric B-ALL. Therefore, validation of these miRNAs in a larger cohort and investigation of their mechanistic role are warranted.

Citation Format: Ernest K. Amankwah, Kelly W. Maloney, Eric C. Larsen, Meenakshi Devidas, David T. Teachey, Karen R. Rabin, Mignon L. Loh, Patrick A. Brown. Identification of six novel candidate miRNAs associated with early relapse in B-cell pediatric acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1576.