학술논문
Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG).
Document Type
Academic Journal
Author
Ozga M; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Nicolet D; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Alliance Statistics and Data Management Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Mrózek K; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. krzysztof.mrozek@osumc.edu.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA. krzysztof.mrozek@osumc.edu.; Yilmaz AS; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Kohlschmidt J; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Alliance Statistics and Data Management Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Larkin KT; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Blachly JS; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Oakes CC; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Buss J; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Walker CJ; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Orwick S; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; Jurinovic V; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Rothenberg-Thurley M; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Dufour A; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Schneider S; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Institute of Human Genetics, University Hospital, LMU Munich, Munich, Germany.; Sauerland MC; Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.; Görlich D; Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany.; Krug U; Department of Medicine 3, Klinikum Leverkusen, Leverkusen, Germany.; Berdel WE; Department of Medicine, Hematology and Oncology, University of Münster, Münster, Germany.; Woermann BJ; German Society of Hematology and Oncology, Berlin, Germany.; Hiddemann W; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Braess J; Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany.; Subklewe M; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Spiekermann K; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Carroll AJ; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA.; Blum WG; Emory University School of Medicine, Atlanta, GA, USA.; Powell BL; Wake Forest University Health Sciences, Winston-Salem, NC, USA.; Kolitz JE; Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA.; Moore JO; Duke Cancer Institute, Duke University Health System, Durham, NC, USA.; Mayer RJ; Department of Medical Oncology, Dana-Farber/Partners CancerCare, Boston, MA, USA.; Larson RA; University of Chicago Medical Center, Chicago, IL, USA.; Uy GL; Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.; Stock W; University of Chicago Medical Center, Chicago, IL, USA.; Metzeler KH; Department of Hematology, Cellular Therapy, and Hemostaseology, Leipzig University Hospital, Leipzig, Germany.; Grimes HL; Division of Immunobiology, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, USA.; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.; Byrd JC; Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.; Salomonis N; Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA.; Division of Biomedical Informatics, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH, USA.; Herold T; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Mims AS; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA.; Eisfeld AK; The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. Ann.Kathrin.Eisfeld@osumc.edu.; The Ohio State University Comprehensive Cancer Center, Clara D. Bloomfield Center for Leukemia Outcomes Research, Columbus, OH, USA. Ann.Kathrin.Eisfeld@osumc.edu.
Source
Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE
Subject
Language
English
Abstract
Clinical outcome of patients with acute myeloid leukemia (AML) is associated with demographic and genetic features. Although the associations of acquired genetic alterations with patients' sex have been recently analyzed, their impact on outcome of female and male patients has not yet been comprehensively assessed. We performed mutational profiling, cytogenetic and outcome analyses in 1726 adults with AML (749 female and 977 male) treated on frontline Alliance for Clinical Trials in Oncology protocols. A validation cohort comprised 465 women and 489 men treated on frontline protocols of the German AML Cooperative Group. Compared with men, women more often had normal karyotype, FLT3-ITD, DNMT3A, NPM1 and WT1 mutations and less often complex karyotype, ASXL1, SRSF2, U2AF1, RUNX1, or KIT mutations. More women were in the 2022 European LeukemiaNet intermediate-risk group and more men in adverse-risk group. We found sex differences in co-occurring mutation patterns and prognostic impact of select genetic alterations. The mutation-associated splicing events and gene-expression profiles also differed between sexes. In patients aged <60 years, SF3B1 mutations were male-specific adverse outcome prognosticators. We conclude that sex differences in AML-associated genetic alterations and mutation-specific differential splicing events highlight the importance of patients' sex in analyses of AML biology and prognostication.
(© 2023. The Author(s).)
(© 2023. The Author(s).)