Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1
| العنوان: | Mutations in DNMT3A, U2AF1, and EZH2 identify intermediate-risk acute myeloid leukemia patients with poor outcome after CR1 |
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| المؤلفون: | Ronald Sobecks, Donna Abounader, Caner Saygin, Aziz Nazha, Cassandra M. Hirsch, Bartlomiej P Przychodzen, Matt Kalaycio, Hetty E. Carraway, Betty K. Hamilton, Sudipto Mukherjee, Anjali S. Advani, Jaroslaw P. Maciejewski, Christopher Goebel, Aaron T. Gerds, Mikkael A. Sekeres |
| المصدر: | Blood Cancer Journal Blood Cancer Journal, Vol 8, Iss 1, Pp 1-12 (2018) |
| بيانات النشر: | Nature Publishing Group UK, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Adult, Male, medicine.medical_specialty, Disease, lcsh:RC254-282, Article, Disease-Free Survival, DNA Methyltransferase 3A, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Text mining, Risk Factors, Internal medicine, hemic and lymphatic diseases, medicine, Humans, Enhancer of Zeste Homolog 2 Protein, DNA (Cytosine-5-)-Methyltransferases, Prospective Studies, Aged, business.industry, EZH2, Cytogenetics, Myeloid leukemia, Hematology, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, Splicing Factor U2AF, 3. Good health, Survival Rate, Leukemia, Leukemia, Myeloid, Acute, 030104 developmental biology, RUNX1, chemistry, 030220 oncology & carcinogenesis, Cohort, Mutation, Female, business |
| الوصف: | Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation. In the CC cohort, median age was 58.5 years, 64% had normal cytogenetics, and 31% required >1 induction cycles to achieve CR1. In univariable analysis, patients carrying mutations in DNMT3A, U2AF1, and EZH2 had worse overall and relapse-free survival. After adjusting for other variables, the presence of these mutations maintained an independent effect on survival in both CC and TCGA cohorts. Patients who did not have the mutations and underwent hematopoietic cell transplant (HCT) had the best outcomes. HCT improved outcomes for patients who had these mutations. RUNX1 or ASXL1 mutations did not predict survival, and performance of HCT did not confer a significant survival benefit. Our results provide evidence of clinical utility in considering mutation screening to stratify IR-AML patients after CR1 to guide therapeutic decisions. |
| اللغة: | English |
| تدمد: | 2044-5385 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eec6fef47c043bea71552ff3ae5f3197Test http://europepmc.org/articles/PMC5802549Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....eec6fef47c043bea71552ff3ae5f3197 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20445385 |
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