Overexpression of LEF1 predicts unfavorable outcome in adult patients with B-precursor acute lymphoblastic leukemia
| العنوان: | Overexpression of LEF1 predicts unfavorable outcome in adult patients with B-precursor acute lymphoblastic leukemia |
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| المؤلفون: | Andrea Kühnl, Liliana H. Mochmann, Claudia D. Baldus, Cornelia Schlee, Martin Kaiser, Eckhard Thiel, Nicola Gökbuget, Wolf-Karsten Hofmann, Dieter Hoelzer, Andrea Stroux, Thomas Burmeister |
| المصدر: | Blood. 118:6362-6367 |
| بيانات النشر: | American Society of Hematology, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Lymphoid Enhancer-Binding Factor 1, Immunology, Bioinformatics, Biochemistry, Cohort Studies, Young Adult, Exon, Mediator, Downregulation and upregulation, Bone Marrow, Recurrence, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Acute lymphocytic leukemia, Internal medicine, Biomarkers, Tumor, medicine, Humans, RNA, Messenger, Young adult, Survival analysis, Aged, business.industry, Remission Induction, Wnt signaling pathway, Exons, Cell Biology, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Neoplasm Proteins, Up-Regulation, Clinical trial, embryonic structures, Female, Mutant Proteins, business |
| الوصف: | Aberrant activation of the Wnt pathway plays a pathogenetic role in various tumors and has been associated with adverse outcome in acute lymphoblastic leukemia (ALL). LEF1, a key mediator of Wnt signaling, has been linked to leukemic transformation, and recurrent mutations of LEF1 have been identified in pediatric T-ALL. Here we evaluated the prognostic significance of LEF1 expression in B-precursor ALL patients. LEF1 expression was determined by quantitative real-time RT-PCR in 282 adult B-precursor ALL patients treated on 06/99 and 07/03 GMALL trials. Patients were grouped into quartiles (Q1-Q4) according to LEF1 expression levels (LEF1 high, Q4; n = 71; LEF1 low, Q1-Q3; n = 211). Patients with high LEF1 expression had a significantly shorter relapse-free survival (RFS) compared with low LEF1 expressers (5-year RFS: LEF1 high, 27%; LEF1 low, 47%; P = .05). Importantly, high LEF1 expression was also associated with inferior RFS in standard-risk patients and was independently predictive for RFS (P = .02) in multivariate analyses for this subgroup. Thus, high LEF1 expression identifies B-precursor ALL patients with inferior RFS, supporting a pathogenetic role of Wnt signaling in ALL. Standard-risk patients with high LEF1 expression might benefit from early treatment modifications and new molecular therapies, including agents targeting the Wnt pathway. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::382039e956cb1231c28fcd80e92c0d28 https://doi.org/10.1182/blood-2011-04-350850 |
| رقم الأكسشن: | edsair.doi.dedup.....382039e956cb1231c28fcd80e92c0d28 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
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