Abstract B86: Ethnic differences in microRNA expression associated with relapse among pediatric B-acute lymphoblastic leukemia patients: A pilot study
Authors: Amankwah Ernest K. , Brown Patrick A. 
Published: February 2019

Introduction: Despite substantial improvements in therapy, approximately 10-20% of pediatric B-acute lymphoblastic leukemia (B-ALL) patients relapse. White Hispanics (WH) have a higher risk of relapse compared to non-Hispanic Whites (NHW). Previous studies suggest a biologic contribution to the disparity, as it persists after controlling for socioeconomic status, medication compliance, and/or minimal residual disease. However, the biologic mechanisms underlying the disparities in relapse are not well understood. In this pilot study, we evaluated the association between relapse risk and microRNA (miRNA) expression among WH and NHW to determine if miRNA expression profile might contribute to the disparity.

Methods: We selected diagnostic leukemia specimens from the Children's Oncology Group biospecimen bank for a cohort of 14 WH and a cohort of 14 NHW pediatric B-ALL patients. Within each cohort, we selected 7 patients in prolonged remission (≥4 years) and 7 patients with relapse within 3 years of diagnosis. The cohorts were matched for age, sex, and cytogenetics. miRNA profiles were generated using the human Affymetrix miRNA 4.0 array (~2,600 miRNAs) and analyzed using BRB-ArrayTools. Within each cohort, we compared global miRNA expression profiles between the 7 remission patients and 7 relapse patients. miRNAs with a fold change &lt;0.67 or &gt;1.5 and a permuted p-value &lt;0.05 were considered to be differentially expressed.

Results: In the WH cohort, we observed differential expression between remission and relapse patients for miR-497-5p, miR-4461, miR-6748-5p, miR-365a-5p, miR-663a, and miR-204-3p. The top differentially expressed miRNA was miR-497-5p (fold=0.4, p=2.0 x 10-4), which is a tumor suppressor that has been implicated in several adult solid tumors. Similarly, miR-365a-5p and miR-663a are tumor suppressors implicated in adult cancers. In the NHW cohort, we observed differential expression for miR-4461, miR-6717-5p, miR-4736, miR-941, miR-501-3p, and miR-29c-3p. The top differentially expressed miRNA was miR-4461 (fold=0.6, p=1.3 x 10-2). miR-4461 was the only one that was differentially expressed among both NHW and WH (fold=0.6, p=3.0 x 10-4).

Conclusion: In this pilot study, the complement of differentially expressed miRNAs associated with subsequent relapse was distinct in the WH cohort compared to the NHW cohort, and included miRNAs with known tumor-suppressor function. Validation of this observation in a larger sample size would suggest that tumor biology, as represented by miRNA expression, may play a role in the disparity of prognosis between Hispanic and non-Hispanic White pediatric B-ALL patients. 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, further evaluation of their role in pediatric B-ALL relapse is warranted.

Citation Format: Ernest K. Amankwah, Patrick A. Brown. Ethnic differences in microRNA expression associated with relapse among pediatric B-acute lymphoblastic leukemia patients: A pilot study [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B86.