title: Preferential occurrence of spliceosome mutations in acute myeloid leukemia with preceding myelodysplastic syndrome and/or myelodysplasia morphology.
abstract: Spliceosome mutations are associated with myelodysplasia. Here, we aimed to evaluate the frequency and clinical associations of these mutations in 204 patients with acute myeloid leukemia with myelodysplasia-related changes (AML with MRC) and 37 with therapy-related AML (t-AML). The frequency of mutation-positive patients was 17.0%, including U2AF1 (8.3%), SRSF2 (5.8%) and SF3B1 (2.9%). Mutations were detected almost exclusively in patients with AML with MRC, especially in cases with a preceding myelodysplastic syndrome (MDS) history or myelodysplastic morphology. By contrast, mutations were rare in patients with only MDS-related cytogenetics or t-AML. The presence of a mutation had no impact on survival. In a paired analysis, 16.7% of mutation-negative patients in the MDS phase acquired mutations during leukemogenesis. Our observations highlight the preponderance of spliceosome mutations within a specific AML subgroup with myelodysplasia, and suggest that these mutations might contribute pathologically to leukemogenesis in such patients.
authors.affiliation: a Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Young-Uk
authors.initials: YU
authors.lastname: Cho
authors.affiliation: a Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Jang
authors.affiliation: a Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Eul-Ju
authors.initials: EJ
authors.lastname: Seo
authors.affiliation: a Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Chan-Jeoung
authors.initials: CJ
authors.lastname: Park
authors.affiliation: a Department of Laboratory Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Chi
authors.affiliation: b Department of Internal Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Dae-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: b Department of Internal Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: b Department of Internal Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.affiliation: b Department of Internal Medicine , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Kyoo-Hyung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: c Department of Pediatrics , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Kyung-Nam
authors.initials: KN
authors.lastname: Koh
authors.affiliation: c Department of Pediatrics , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Ho-Joon
authors.initials: HJ
authors.lastname: Im
authors.affiliation: c Department of Pediatrics , University of Ulsan College of Medicine and Asan Medical Center , Seoul , Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Seo
authors.affiliation: d Department of Laboratory Medicine , Pusan National University School of Medicine , Pusan , Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: e Asan Institute for Life Sciences, University of Ulsan College of Medicine , Seoul , Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Park
authors.affiliation: e Asan Institute for Life Sciences, University of Ulsan College of Medicine , Seoul , Korea.
authors.forename: Jong-Keuk
authors.initials: JK
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D017381:Spliceosomes / Q000235:genetics*; D016019:Survival Analysis; D055815:Young Adult
keywords: Acute myeloid leukemia; MDS-related cytogenetics; myelodysplastic syndrome; spliceosome mutation