Deregulated Expression of EVI1 Defines a Poor Prognostic Subset of MLL-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group
| Autor: | Michael Lübbert, Karina Eiwen, Gerrit Jan Schuurhuis, Brigitte Schlegelberger, Claudia Erpelinck, Jan Engelmann, Arnold Ganser, Veronika Rockova, Hartmut Döhner, Mario Bargetzi, Ulrich Germing, H. Berna Beverloo, Ruud Delwel, Peter Vandenberghe, Peter J. M. Valk, Veronica Teleanu, Stefan Gröschel, Ingo G.H. Schmidt-Wolf, Richard F. Schlenk, Jürgen Krauter, Bob Löwenberg, Marije Havermans, Edo Vellenga, Leo F. Verdonck, Thomas Pabst, Gert J. Ossenkoppele, Gregor Verhoef, Michael W.M. Kühn, Konstanze Döhner |
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| Přispěvatelé: | Hematology laboratory, Hematology, CCA - Disease profiling, Faculteit Medische Wetenschappen/UMCG, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, Clinical Genetics |
| Rok vydání: | 2013 |
| Předmět: |
Oncology
Male Cancer Research Myeloid Translocation Genetic 0302 clinical medicine hemic and lymphatic diseases Medicine ADULT PATIENTS Prospective Studies Acute myeloid leukemias Gene Rearrangement 0303 health sciences ABNORMALITIES Remission Induction Myeloid leukemia Middle Aged Prognosis 3. Good health DNA-Binding Proteins Survival Rate MLL gene rearrangements Leukemia Leukemia Myeloid Acute medicine.anatomical_structure 030220 oncology & carcinogenesis TRIAL Female Viral integration Chromosomes Human Pair 9 Myeloid-Lymphoid Leukemia Protein Adult medicine.medical_specialty Adolescent MLL-AF9 03 medical and health sciences Young Adult Internal medicine Proto-Oncogenes Cooperative group Humans 60 YEARS OLD TRANSLOCATIONS neoplasms 030304 developmental biology Aged Neoplasm Staging Chromosome Aberrations TET2 MUTATIONS business.industry Chromosomes Human Pair 11 Gene rearrangement Histone-Lysine N-Methyltransferase medicine.disease GENE TRANSFORMATION MDS1 and EVI1 Complex Locus Protein Karyotyping Immunology business Follow-Up Studies Transcription Factors |
| Zdroj: | Journal of Clinical Oncology, 31(1), 95-103. American Society of Clinical Oncology Groschel, S, Schlenk, R F, Engelmann, J, Rockova, V, Teleanu, V, Kuhn, M W M, Eiwen, K, Erpelinck, C, Havermans, M, Lubbert, M, Germing, U, Schmidt-Wolf, I G H, Beverloo, HB, Schuurhuis, G J, Ossenkoppele, G J, Schlegelberger, B, Verdonck, L F, Vellenga, E, Verhoef, G, Vandenberghe, P, Pabst, T, Bargetzi, M, Krauter, J, Ganser, A, Valk, P J M, Lowenberg, B, Dohner, K, Dohner, H & Delwel, R 2013, ' Deregulated Expression of EVI1 Defines a Poor Prognostic Subset of MLL-Rearranged Acute Myeloid Leukemias: A Study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group ', Journal of Clinical Oncology, vol. 31, no. 1, pp. 95-103 . https://doi.org/10.1200/JCO.2011.41.5505 Journal of Clinical Oncology, 31(1), 95-103. AMER SOC CLINICAL ONCOLOGY Journal of clinical oncology : official journal of the American Society of Clinical Oncology |
| ISSN: | 0732-183X |
| Popis: | Purpose To evaluate the prognostic value of ecotropic viral integration 1 gene (EVI1) overexpression in acute myeloid leukemia (AML) with MLL gene rearrangements. Patients and Methods We identified 286 patients with AML with t(11q23) enrolled onto German-Austrian Acute Myeloid Leukemia Study Group and Dutch-Belgian-Swiss Hemato-Oncology Cooperative Group prospective treatment trials. Material was available from 177 AML patients for EVI1 expression analysis. Results We divided 286 MLL-rearranged AMLs into three subgroups: t(9;11)(p22;q23) (44.8%), t(6;11)(q27;q23) (14.7%), and t(v;11q23) (40.5%). EVI1 overexpression (EVI1+) was found in 45.8% of all patients with t(11q23), with t(6;11) showing the highest frequency (83.9%), followed by t(9;11) at 40.0%, and t(v;11q23) at 34.8%. Concurrent gene mutations were rare or absent in all three subgroups. Within all t(11q23) AMLs, EVI1+ was the sole prognostic factor, predicting for inferior overall survival (OS; hazard ratio [HR], 2.06; P = .003), relapse-free survival (HR, 2.28; P = .002), and event-free survival (HR, 1.79; P = .009). EVI1+ AMLs with t(11q23) in first complete remission (CR) had a significantly better outcome after allogeneic transplantation compared with other consolidation therapies (5-year OS, 54.7% v 0%; Mantel-Byar, P = .0006). EVI1− t(9;11) AMLs had lower WBC counts, more commonly FAB M5 morphology, and frequently had additional trisomy 8 (39.6%; P < .001). Among t(9;11) AMLs, EVI1+ again was the sole independent adverse prognostic factor for survival. Conclusion Deregulated EVI1 expression defines poor prognostic subsets among AML with t(11q23) and AML with t(9;11)(p22;q23). Patients with EVI1+ MLL-rearranged AML seem to benefit from allogeneic transplantation in first CR. |
| Databáze: | OpenAIRE |
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