دورية أكاديمية
Simpson's Paradox and the Impact of Different DNMT3A Mutations on Outcome in Younger Adults With Acute Myeloid Leukemia.
| العنوان: | Simpson's Paradox and the Impact of Different DNMT3A Mutations on Outcome in Younger Adults With Acute Myeloid Leukemia. |
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| المؤلفون: | Gale RE; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom. rosemary.gale@ucl.ac.uk., Lamb K; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Allen C; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., El-Sharkawi D; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Stowe C; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Jenkinson S; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Tinsley S; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Dickson G; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Burnett AK; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Hills RK; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom., Linch DC; Rosemary E. Gale, Katarina Lamb, Christopher Allen, Dima El-Sharkawi, Cassandra Stowe, Sarah Jenkinson, Steven Tinsley, Glenda Dickson, and David C. Linch, University College London Cancer Institute, London; and Alan K. Burnett and Robert K. Hills, Cardiff University School of Medicine, Cardiff, United Kingdom. |
| المصدر: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2015 Jun 20; Vol. 33 (18), pp. 2072-83. Date of Electronic Publication: 2015 May 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 8309333 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-7755 (Electronic) Linking ISSN: 0732183X NLM ISO Abbreviation: J Clin Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2003- : Alexandria, VA : American Society of Clinical Oncology Original Publication: New York, N.Y. : Grune & Stratton, c1983- |
| مواضيع طبية MeSH: | Mutation*, DNA (Cytosine-5-)-Methyltransferases/*genetics , Leukemia, Myeloid, Acute/*genetics, Adolescent ; Adult ; Age Factors ; Aged ; Cohort Studies ; CpG Islands ; DNA Methyltransferase 3A ; DNA Mutational Analysis ; Exons ; Female ; Genotype ; Humans ; Incidence ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Nucleophosmin ; Prognosis ; Proportional Hazards Models ; Treatment Outcome ; Young Adult |
| مستخلص: | Purpose: To evaluate the impact of DNMT3A mutations on outcome in younger patients with cytogenetic intermediate-risk acute myeloid leukemia. Patients and Methods: Diagnostic samples from 914 patients (97% < 60 years old) were screened for mutations in DNMT3A exons 13 to 23. Clinical outcome was evaluated according to presence or absence of a mutation and stratified according to type of mutation (R882, non-R882 missense, or truncation). Results: DNMT3A mutations (DNMT3A(MUT)) were identified in 272 patients (30%) and associated with a poorer prognosis than wild-type DNMT3A, but the difference was only seen when the results were stratified according to NPM1 genotype. This example of Simpson's paradox results from the high coincidence of DNMT3A and NPM1 mutations (80% of patients with DNMT3A(MUT) had NPM1 mutations), where the two mutations have opposing prognostic impact. In the stratified analyses, relapse in patients with DNMT3A(MUT) was higher (hazard ratio, 1.35; 95% CI, 1.07 to 1.72; P = .01), and overall survival was lower (hazard ratio, 1.37; 95% CI, 1.12 to 1.87; P = .002). The impact of DNMT3A(MUT) did not differ according to NPM1 genotype (test for heterogeneity: relapse, P = .4; overall survival, P = .9). Further analysis according to the type of DNMT3A mutation indicated that outcome was comparable in patients with R882 and non-R882 missense mutants, whereas in those with truncation mutants, it was comparable to wild-type DNMT3A. Conclusion: These data confirm that presence of a DNMT3A mutation should be considered as a poor-risk prognostic factor, irrespective of the NPM1 genotype, and suggest that further consideration should be given to the type of DNMT3A mutation. (© 2015 by American Society of Clinical Oncology.) |
| معلومات مُعتمدة: | 15556 United Kingdom CRUK_ Cancer Research UK; United Kingdom MRC_ Medical Research Council; United Kingdom DH_ Department of Health |
| المشرفين على المادة: | 0 (DNMT3A protein, human) 0 (NPM1 protein, human) 117896-08-9 (Nucleophosmin) EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) EC 2.1.1.37 (DNA Methyltransferase 3A) |
| تواريخ الأحداث: | Date Created: 20150513 Date Completed: 20150831 Latest Revision: 20240210 |
| رمز التحديث: | 20240210 |
| DOI: | 10.1200/JCO.2014.59.2022 |
| PMID: | 25964253 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1527-7755 |
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| DOI: | 10.1200/JCO.2014.59.2022 |