title: Circulating miRNA panel for prediction of acute graft-versus-host disease in lymphoma patients undergoing matched unrelated hematopoietic stem cell transplantation.
abstract: Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Noninvasive diagnostic and prognostic tests for aGVHD are currently lacking, but would be beneficial in predicting aGVHD and improving the safety of allo-HSCT. Circulating microRNAs exhibit marked stability and may serve as biomarkers in several clinical settings. Here, we evaluated the use of circulating microRNAs as predictive biomarkers of aGVHD in lymphoma patients after allo-HSCT from matched unrelated donors (MUDs). After receiving informed consent, we prospectively collected plasma samples from 24 lymphoma patients before and after unmanipulated MUD allo-HSCT; microRNAs were then isolated. Fourteen patients developed aGVHD symptoms at a median of 48 days (range: 32-90) post-transplantation. Two patients developed intestinal GVHD, eight cutaneous GVHD, and four multiorgan GVHD. The microRNA expression profile was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MicroRNAs 194 and 518f were significantly upregulated in aGVHD samples compared with samples taken from non-aGVHD patients. Remarkably, these upregulated microRNAs could be detected before the onset of aGVHD. Pathway prediction analysis indicated that these microRNAs may regulate critical pathways involved in aGVHD pathogenesis. Considering the noninvasive characteristics of plasma sampling and the feasibility of detecting miRNAs after allo-HSCT using real-time polymerase chain reaction, our results indicate that circulating microRNAs have the potential to enable an earlier aGVHD diagnosis and might assist in individualizing therapeutic strategies after MUD allo-HSCT. Nevertheless, standardization of blood sampling and analysis protocols is mandatory for the introduction of miRNA profiling into routine clinical use.
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Hematology, Department of Oncology and Onco-Hematology, Università degli Studi di Milano, Milan, Italy. Electronic address: silvia.gimondi@unimi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gimondi
authors.affiliation: Functional Genomics Core Facility, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Dugo
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Hematology, Department of Oncology and Onco-Hematology, Università degli Studi di Milano, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vendramin
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Anisa
authors.initials: A
authors.lastname: Bermema
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Biancon
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cavané
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Hematology, Department of Oncology and Onco-Hematology, Università degli Studi di Milano, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
authors.affiliation: Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Cristiana
authors.initials: C
authors.lastname: Carniti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D016000:Cluster Analysis; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008223:Lymphoma / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D013997:Time Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs