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Title: 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
Authors: Gröschel, Stefan ×
Schlenk, Richard F
Engelmann, Jan
Rockova, Veronika
Teleanu, Veronica
Kühn, Michael W M
Eiwen, Karina
Erpelinck, Claudia
Havermans, Marije
Lübbert, Michael
Germing, Ulrich
Schmidt-Wolf, Ingo G H
Beverloo, H Berna
Schuurhuis, Gerrit J
Ossenkoppele, Gert J
Schlegelberger, Brigitte
Verdonck, Leo F
Vellenga, Edo
Verhoef, Gregor
Vandenberghe, Peter
Pabst, Thomas
Bargetzi, Mario
Krauter, Jürgen
Ganser, Arnold
Valk, Peter J M
Löwenberg, Bob
Döhner, Konstanze
Döhner, Hartmut
Delwel, Ruud #
Issue Date: Jan-2013
Publisher: Grune & Stratton
Series Title: Journal of Clinical Oncology vol:31 issue:1 pages:95-103
Article number: 10.1200/JCO.2011.41.5505
Abstract: 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.
URI: 
ISSN: 0732-183X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Cell and Gene Therapy Applications (-)
× corresponding author
# (joint) last author

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