title: MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia.
abstract: Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders of the elderly that carry an increased risk of progression to acute myeloid leukemia (AML). Since small non-coding RNAs (sRNAs), including microRNA (miRNAs), act as regulators of cellular differentiation, we hypothesized that changes to sRNAs might be implicated in the progression of MDS to AML. We conducted sRNA sequencing on three sets of patients: Group A (MDS patients who never progressed to AML); Group B (MDS patients who later progressed to an AML); and Group C (AML patients with myelodysplasia-related changes, including patients with a known preceding diagnosis of MDS). We identified five miRNAs that differentiated Groups A and B, independent of bone marrow blast percentage, including three members of the miR-181 family, as well as differential patterns of miRNA isoforms (isomiRs) and tDRs. Thus, we have identified sRNA biomarkers that predict MDS cases that are likely to progress to AML.
authors.affiliation: a Center for Quantitative Sciences , Vanderbilt University , Nashville , TN , USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: b Department of Medicine, Division of Hematology/Oncology , Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Strickland
authors.affiliation: b Department of Medicine, Division of Hematology/Oncology , Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mohan
authors.affiliation: c Hematopathology Department , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Li
authors.affiliation: d Department of Pathology , Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Amma
authors.initials: A
authors.lastname: Bosompem
authors.affiliation: e Department of Medicine , Vanderbilt University Medical Center , Nashville , TN , USA.
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.affiliation: f Department of Cancer Biology , Vanderbilt University , Nashville , TN , USA.
authors.forename: Shilin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: f Department of Cancer Biology , Vanderbilt University , Nashville , TN , USA.
authors.forename: Quanhu
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: g Department of Pathology, Brigham and Women's Hospital , Boston , MA , USA.
authors.forename: Annette S
authors.initials: AS
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012343:RNA, Transfer / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012343:RNA, Transfer
keywords: Myeloid leukemias and dysplasias; molecular genetics; prognostication