title: Serum Exosome MicroRNA as a Minimally-Invasive Early Biomarker of AML.
abstract: 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, we 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. We 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. We propose development of serum exosome miRNA as a platform for a novel, sensitive compartment biomarker for prospective tracking and early detection of AML recurrence.
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Noah I
authors.initials: NI
authors.lastname: Hornick
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Jianya
authors.initials: J
authors.lastname: Huan
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Ben
authors.initials: B
authors.lastname: Doron
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Natalya A
authors.initials: NA
authors.lastname: Goloviznina
authors.affiliation: Department of Public Health, Oregon Health &Science University, Portland, OR.
authors.forename: Jodi
authors.initials: J
authors.lastname: Lapidus
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR [4] Knight Cancer Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Bill H
authors.initials: BH
authors.lastname: Chang
authors.affiliation: 1] Department of Pediatrics, Oregon Health &Science University, Portland, OR [2] Department of Medicine, Oregon Health &Science University, Portland, OR [3] Papé Family Pediatric Research Institute, Oregon Health &Science University, Portland, OR [4] Knight Cancer Institute, Oregon Health &Science University, Portland, OR.
authors.forename: Peter
authors.initials: P
authors.lastname: Kurre
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D055354:Exosomes / Q000378:metabolism*; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000097:blood*; D009374:Neoplasms, Experimental / Q000097:blood* / Q000473:pathology; D012334:RNA, Neoplasm / Q000097:blood*; D020298:U937 Cells
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm