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 , Volume 31 - Issue 1 p. 95- 103
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.
|Journal of Clinical Oncology|
|Organisation||Department of Clinical Genetics|
Gröschel, S, Schlenk, R.F, Engelmann, J, Rockova, V, Teleanu, V, Kühn, M.W.M, … Delwel, H.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, 31(1), 95–103. doi:10.1200/JCO.2011.41.5505