Johann-Christoph Jann, Christopher B. Hergott, Marisa Winkler, Yiwen Liu, Benjamin Braun, Anne Charles, Kevin M. Copson, Shougat Barua, Manja Meggendorfer, Niroshan Nadarajah, Shai Shimony, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Daniel J. DeAngelo, Jacqueline S. Garcia, Torsten Haferlach, R. Coleman Lindsley, Marlise R. Luskin, Maximilian Stahl, Zuzana Tothova
{"title":"对粘合素突变的髓系恶性肿瘤进行亚基特异性分析,揭示了不同的本体发生和结局","authors":"Johann-Christoph Jann, Christopher B. Hergott, Marisa Winkler, Yiwen Liu, Benjamin Braun, Anne Charles, Kevin M. Copson, Shougat Barua, Manja Meggendorfer, Niroshan Nadarajah, Shai Shimony, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Daniel J. DeAngelo, Jacqueline S. Garcia, Torsten Haferlach, R. Coleman Lindsley, Marlise R. Luskin, Maximilian Stahl, Zuzana Tothova","doi":"10.1038/s41375-024-02347-y","DOIUrl":null,"url":null,"abstract":"Mutations in the cohesin complex components (STAG2, RAD21, SMC1A, SMC3, and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies. We found that STAG2 mutations are acquired at MDS stage and are associated with secondary AML, adverse prognosis, and co-occurrence of secondary AML-type mutations. In contrast, mutations in RAD21, SMC1A and SMC3 share features with de novo AML with better prognosis, and co-occurrence with de novo AML-type lesions. The findings show the heterogeneous nature of cohesin complex mutations, and inform clinical and prognostic classification, as well as distinct biology of the cohesin complex.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":null,"pages":null},"PeriodicalIF":12.8000,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02347-y.pdf","citationCount":"0","resultStr":"{\"title\":\"Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes\",\"authors\":\"Johann-Christoph Jann, Christopher B. Hergott, Marisa Winkler, Yiwen Liu, Benjamin Braun, Anne Charles, Kevin M. Copson, Shougat Barua, Manja Meggendorfer, Niroshan Nadarajah, Shai Shimony, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Daniel J. DeAngelo, Jacqueline S. Garcia, Torsten Haferlach, R. Coleman Lindsley, Marlise R. Luskin, Maximilian Stahl, Zuzana Tothova\",\"doi\":\"10.1038/s41375-024-02347-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Mutations in the cohesin complex components (STAG2, RAD21, SMC1A, SMC3, and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies. We found that STAG2 mutations are acquired at MDS stage and are associated with secondary AML, adverse prognosis, and co-occurrence of secondary AML-type mutations. In contrast, mutations in RAD21, SMC1A and SMC3 share features with de novo AML with better prognosis, and co-occurrence with de novo AML-type lesions. The findings show the heterogeneous nature of cohesin complex mutations, and inform clinical and prognostic classification, as well as distinct biology of the cohesin complex.\",\"PeriodicalId\":18109,\"journal\":{\"name\":\"Leukemia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.8000,\"publicationDate\":\"2024-07-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s41375-024-02347-y.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Leukemia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.nature.com/articles/s41375-024-02347-y\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Leukemia","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41375-024-02347-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes
Mutations in the cohesin complex components (STAG2, RAD21, SMC1A, SMC3, and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies. We found that STAG2 mutations are acquired at MDS stage and are associated with secondary AML, adverse prognosis, and co-occurrence of secondary AML-type mutations. In contrast, mutations in RAD21, SMC1A and SMC3 share features with de novo AML with better prognosis, and co-occurrence with de novo AML-type lesions. The findings show the heterogeneous nature of cohesin complex mutations, and inform clinical and prognostic classification, as well as distinct biology of the cohesin complex.
期刊介绍:
Title: Leukemia
Journal Overview:
Publishes high-quality, peer-reviewed research
Covers all aspects of research and treatment of leukemia and allied diseases
Includes studies of normal hemopoiesis due to comparative relevance
Topics of Interest:
Oncogenes
Growth factors
Stem cells
Leukemia genomics
Cell cycle
Signal transduction
Molecular targets for therapy
And more
Content Types:
Original research articles
Reviews
Letters
Correspondence
Comments elaborating on significant advances and covering topical issues