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

被引：76

作者：

Groeschel, Stefan ^{[1
]}

Schlenk, Richard F. ^{[1
]}

Engelmann, Jan ^{[1
]}

Rockova, Veronika ^{[6
]}

Teleanu, Veronica ^{[1
]}

Kuehn, Michael W. M. ^{[1
]}

Eiwen, Karina ^{[1
]}

Erpelinck, Claudia ^{[6
]}

Havermans, Marije ^{[6
]}

Luebbert, Michael ^{[2
]}

Germing, Ulrich ^{[3
]}

Schmidt-Wolf, Ingo G. H. ^{[4
]}

Beverloo, H. Berna ^{[6
]}

Schuurhuis, Gerrit J. ^{[7
]}

Ossenkoppele, Gert J. ^{[7
]}

Schlegelberger, Brigitte ^{[5
]}

Verdonck, Leo F. ^{[8
]}

Vellenga, Edo ^{[9
]}

Verhoef, Gregor ^{[10
]}

Vandenberghe, Peter ^{[10
]}

Pabst, Thomas ^{[11
]}

Bargetzi, Mario ^{[12
]}

Krauter, Juegen ^{[5
]}

Ganser, Arnold ^{[5
]}

Valk, Peter J. M. ^{[6
]}

Lowenberg, Bob ^{[6
]}

Doehner, Konstanze ^{[1
]}

Doehner, Hartmut ^{[1
]}

Delwel, Ruud

机构：

[1] Univ Hosp Ulm, Ulm, Germany

[2] Univ Freiburg, Med Ctr, Freiburg, Germany

[3] Univ Dusseldorf, D-40225 Dusseldorf, Germany

[4] Univ Bonn, Bonn, Germany

[5] Hannover Med Sch, Hannover, Germany

[6] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands

[7] Vrije Univ, Med Ctr, Amsterdam, Netherlands

[8] Isala Clin, Zwolle, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands

[10] Univ Hosp Leuven, unihos, Louvain, Belgium

[11] Univ Hosp Bern, CH-3010 Bern, Switzerland

[12] Kantonsspital, Aarau, Switzerland

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2013年 / 31卷 / 01期

关键词：

60 YEARS OLD; ADULT PATIENTS; GENE; MUTATIONS; TRANSLOCATIONS; TRANSFORMATION; MLL-AF9; TET2;

D O I：

10.1200/JCO.2011.41.5505

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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% v0%; 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. J Clin Oncol 31:95-103. (c) 2012 by American Society of Clinical Oncology

引用

页码：95 / 103

页数：9

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