title: Impact of allogeneic hematopoietic cell transplant in patients with myeloid neoplasms carrying spliceosomal mutations.
abstract: Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations in the spliceosomal genes (U2AF1 and SRSF2) predict for poor outcomes in myelodysplastic syndromes (MDS) and related diseases. We investigated the effect of hematopoietic cell transplant (HCT) on the negative prognostic impact of U2AF1 and SRSF2 mutations. In total, 122 patients with MDS (30%), acute myeloid leukemia (51%), myeloproliferative neoplasms (MPN) (11%), and MDS/MPN (8%) receiving a HCT from 2003 to 2012 were evaluated for mutations in U2AF1 and SRSF2 by direct sequencing. Median time of follow up was 24 months (range 0.46-110). SRSF2 mutations were detected in 11 (10%) patients and U2AF1 in 3 (3%) patients. There were no significant differences in baseline characteristics between mutated and wild-type (WT) patients. Patients carrying SRSF2 and U2AF1 mutations had similar overall survival (P = 0.84), relapse mortality (P = 0.50), and non-relapse mortality (P = 0.72) compared to WT patients. However, taking into account disease status and cytogenetics in a subset of AML patients, SRSF2 and U2AF1 mutations were associated with worse survival (HR 3.71, P = 0.035).
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Betty Ky
authors.initials: BK
authors.lastname: Hamilton
authors.affiliation: Department of Translational Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Valeria
authors.initials: V
authors.lastname: Visconte
authors.affiliation: Department of Quantitative Health Sciences, Cleveland Clinic Lerner Research Institute, Cleveland, Ohio.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Translational Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Ali
authors.initials: A
authors.lastname: Tabarroki
authors.affiliation: Department of Translational Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Hideki
authors.initials: H
authors.lastname: Makishima
authors.affiliation: Department of Translational Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Edy
authors.initials: E
authors.lastname: Hasrouni
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Donna
authors.initials: D
authors.lastname: Abounader
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Matt
authors.initials: M
authors.lastname: Kalaycio
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Mikkael A
authors.initials: MA
authors.lastname: Sekeres
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Ronald
authors.initials: R
authors.lastname: Sobecks
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Hien
authors.initials: H
authors.lastname: Duong Liu
authors.affiliation: Blood and Marrow Transplant Program, Department of Hematology and Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Brian
authors.initials: B
authors.lastname: Bolwell
authors.affiliation: Department of Translational Hematology and Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio.
authors.forename: Jaroslaw P
authors.initials: JP
authors.lastname: Maciejewski
authors.affiliation: Department of Hematology and Medical Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina.
authors.forename: Edward
authors.initials: E
authors.lastname: Copelan
authors.affiliation: Early Phase Oncology, Eli-Lilly and Company, Indianapolis, Indiana.
authors.forename: Ramon V
authors.initials: RV
authors.lastname: Tiu
mesh_terms: D005091:Exons; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000235:genetics; D011379:Prognosis; D012261:Ribonucleoproteins / Q000235:genetics; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000235:genetics*; D000072668:Splicing Factor U2AF; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors