Abstract 1173: Disparity in pediatric B-cell acute lymphoblastic leukemia relapse between Hispanics and Non-Hispanic Whites: A potential role of miR-3158-3p
Authors: Amankwah Ernest K. , Berglund Anders , Rabin Karen , Brown Patrick A. , Park Jong Y. 
Published: September 2020

Background: Hispanics (HSP) have a higher risk of pediatric acute lymphoblastic leukemia (ALL) relapse compared to Non-Hispanic Whites (NHW). Although previous studies suggest a biological contribution to the ethnic disparity, the biological mechanism is not fully elucidated. In this study, we evaluated the potential role of miRNAs in the disparity of pediatric B-ALL early relapse in a two-stage pilot study.

Methods: We first performed a discovery phase on 14 HSP (7 relapse and 7 remission) and 14 NHW (7 relapse and 7 remission) preselected initial diagnostic B-ALL, minimal residual disease negative specimens without adverse cytogenetic features. Global miRNA expression profiles were compared between remission and relapse patients in the combined sample (14 relapse vs 14 remission) and between ethnic groups (14 HSP vs 14 NHW). We then selected candidate miRNAs that were differentially expressed between combined remission and relapse samples as well as between HSP and NHW for validation. Validation and expression of candidate miRNAs within each ethnic group were performed on a publicly available data from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) program using 22 HSP (12 relapse and 10 remission) and 71 NHW (39 relapse and 32 remission) that had miRNA-seq, ethnicity and relapse data available.

Results: In the discovery phase, miR-3158-3p, miR-378j and miR-4642 were differentially expressed between remission and relapse samples as well as between HSP and NHW. The expressions of miR-3158-3p (fold change (FC)=0.87, p=0.046), and miR-378j (FC=0.85, p=0.043) were decreased in relapse compared to remission patients, but the decrease was more prominent in NHW (miR-3158-3p: FC=0.83, p=0.047 and miR-378j: FC=0.81, p=0.077) than HSP (miR-3158-3p: FC=0.91, p=0.35 and miR-378j: FC=0.89, p=0.18). In contrast, the expression of miR-4642 was elevated (FC=1.29, p=0.011) in relapse compared to remission patients, but the elevation was more prominent in HSP (FC=1.58, p=0.005) than NHW (FC=1.04, p=0.51). In addition, miR-3158-3p (FC=0.87, p=0.040) and miR-4642 (FC=0.81, p=0.047) were under-expressed in NHW compared to HSP, while miR-378j (FC=1.23, p=0.013) was overexpressed in NHW compared to HSP. The under-expression of miR-3158-3p in relapse compared to remission samples (NHW: FC=0.75, p=0.007; overall: FC=0.86, p=0.07) was validated in the independent TARGET dataset. In silico analysis using DIANA microT predicted that miR-3158-3p targeted three genes, SMAD4, SHC and NFKB1, that are implicated in leukemia.

Conclusion: This study adds to the accumulating evidence that miRNAs have critical roles in pediatric B-ALL relapse and provides preliminary evidence, for the first time, that miRNA expression may contribute to the ethnic disparity in pediatric B-ALL relapse. However, these findings need to be validated in a larger cohort and the biological role of the miRNAs in the disparity of pediatric B-ALL relapse needs to be elucidated.

Citation Format: Ernest K. Amankwah, Anders Berglund, Karen Rabin, Patrick A. Brown, Jong Y. Park. Disparity in pediatric B-cell acute lymphoblastic leukemia relapse between Hispanics and Non-Hispanic Whites: A potential role of miR-3158-3p [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1173.