Molecular and clinical features of myeloid neoplasms with somatic DDX41 mutations
Summary We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinica...
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| Published in | British journal of haematology Vol. 192; no. 6; pp. 1006 - 1010 |
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| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Blackwell Publishing Ltd
01.03.2021
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| Abstract | Summary
We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two‐year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. |
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| AbstractList | Summary
We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two‐year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two‐year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two-year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. Summary We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two‐year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T, p.T360Ifs*33, p.V152G, p.S217Ifs*4, p.R311* and p.R369*. Except for the p.R369*, no other variants have been previously reported. Clinical covariates of subjects with simple DDX41 somatic variants and germline/somatic biallelic variants are similar. The two-year overall survival (OS) of subjects with DDX41 variants was 85%. Overall response rate to demethylation therapy in subjects with DDX41 variants was 69%. The response did not correlate with the presence of a germline variant. |
| Author | Qin, Tiejun Xu, Zefeng Xiao, Zhijian Peter Gale, Robert Huang, Gang Hu, Naibo Qu, Shiqiang Li, Bing Pan, Lijuan |
| AuthorAffiliation | 5 Haematology Section, Department of Immunology and Inflammation, Imperial College London, London, UK 4 Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 1 MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China 3 National Clinical Research Centre for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China 2 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China |
| AuthorAffiliation_xml | – name: 1 MDS and MPN Centre, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China – name: 2 State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China – name: 3 National Clinical Research Centre for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China – name: 4 Divisions of Pathology and Experimental Hematology and Cancer Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA – name: 5 Haematology Section, Department of Immunology and Inflammation, Imperial College London, London, UK |
| Author_xml | – sequence: 1 givenname: Shiqiang surname: Qu fullname: Qu, Shiqiang organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 2 givenname: Bing surname: Li fullname: Li, Bing organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 3 givenname: Tiejun surname: Qin fullname: Qin, Tiejun organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 4 givenname: Zefeng surname: Xu fullname: Xu, Zefeng organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 5 givenname: Lijuan surname: Pan fullname: Pan, Lijuan organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 6 givenname: Naibo surname: Hu fullname: Hu, Naibo organization: Chinese Academy of Medical Sciences and Peking Union Medical College – sequence: 7 givenname: Gang surname: Huang fullname: Huang, Gang organization: Cincinnati Children's Hospital Medical Center – sequence: 8 givenname: Robert surname: Peter Gale fullname: Peter Gale, Robert organization: Imperial College London – sequence: 9 givenname: Zhijian surname: Xiao fullname: Xiao, Zhijian email: zjxiao@ihcams.ac.cn organization: Chinese Academy of Medical Sciences and Peking Union Medical College |
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| Cites_doi | 10.1038/leu.2016.124 10.1038/leu.2016.310 10.1182/blood-2015-10-676098 10.1016/j.ccell.2015.03.017 10.1007/s12185-017-2260-y 10.1002/ajh.25610 10.1002/ajh.25486 10.1002/gcc.22510 10.1038/leu.2016.228 10.3324/haematol.2015.139790 10.1182/blood.2019000909 10.1182/blood-2016-03-643544 10.1016/j.exphem.2016.04.017 |
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| Keywords | genetic predisposition DDX41 variants demethylation therapy myelodysplastic syndromes |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Z.J.X. designed the research, was the principal investigator, and took primary responsibility for the paper; S.Q.Q., B.L. and Z.J.X. acquired the data, analysed and interpreted the data, performed statistical analysis and drafted the article; S.Q.Q., T.J.Q., Z.F.X, B.L., L.J.P., N.B.H., and Z.J.X. recruited the patients; Z.J.X., G.H. and R.P.G. prepared the manuscript. Author contributions |
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| References | 2016; 101 2016; 30 2017; 31 2016; 127 2015; 27 2015 2019; 94 2020; 95 2019; 134 2017; 106 2018; 57 2016; 44 e_1_2_6_9_1 Takeda J (e_1_2_6_10_1) 2015 e_1_2_6_8_1 e_1_2_6_5_1 e_1_2_6_4_1 e_1_2_6_7_1 e_1_2_6_6_1 e_1_2_6_13_1 e_1_2_6_14_1 e_1_2_6_3_1 e_1_2_6_11_1 e_1_2_6_2_1 e_1_2_6_12_1 e_1_2_6_15_1 |
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We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T,... We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T,... Summary We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T,... We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T,... We screened 47 subjects with DDX41 variants among 1529 subjects with myeloid neoplasms. The most common germline variants included Splice c.935 + 4A>T,... |
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| SubjectTerms | DDX41 variants Demethylation demethylation therapy genetic predisposition Hematology myelodysplastic syndromes Tumors |
| Title | Molecular and clinical features of myeloid neoplasms with somatic DDX41 mutations |
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