Relapse remains the major cause of mortality for patients with Acute Myeloid Leukemia (AML). Improved tracking of minimal residual disease (MRD) holds the promise of timely treatment adjustments to preempt relapse. Current surveillance techniques detect circulating blasts that coincide with advanced disease and poorly reflect MRD during early relapse.
Here, researchers from the Oregon Health &Science University investigate exosomes as a minimally invasive platform for a microRNA (miRNA) biomarker. We identify a set of miRNA enriched in AML exosomes and track levels of circulating exosome miRNA that distinguish leukemic xenografts from both non-engrafted and human CD34+ controls. They develop biostatistical models that reveal circulating exosomal miRNA at low marrow tumor burden and before circulating blasts can be detected. Remarkably, both leukemic blasts and marrow stroma contribute to serum exosome miRNA. The researchers propose development of serum exosome miRNA as a platform for a novel, sensitive compartment biomarker for prospective tracking and early detection of AML recurrence.
(a,b) RNA size profiles of exosomes. RNA was collected from Molm-14 (a) and NSG Stromal (b) cells and their exosomes after 72 hours in culture, and miRNA was evaluated using a bioanalyzer. (c) Microarray comparison of cell, exosome miRNA. Molm-14 cell and exosome microRNA was evaluated using an Affymetrix microRNA microarray. All targets with more than 2-fold mean difference between producing cell and exosome are represented, RMA-corrected and standardized to a mean of 0 and a SD of 1. Dendrogram values are 1 – Pearson’s R. (d,e) qRT-PCR for miRNA in cells versus exosomes. Selected targets from NSG stromal (d) and Molm-14 (e) cells and exosomes were validated using Taqman qRT-PCR, normalized to U6 snRNA. Fold change was calculated by 2^-ΔΔCt.