Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2012
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.
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAdultAgedChromosome AberrationsChromosomes, Human, Pair 11Chromosomes, Human, Pair 9DNA-Binding ProteinsFemaleFollow-Up StudiesGene RearrangementHistone-Lysine N-MethyltransferaseHumansKaryotypingLeukemia, Myeloid, AcuteMDS1 and EVI1 Complex Locus ProteinMaleMiddle AgedMyeloid-Lymphoid Leukemia ProteinNeoplasm StagingPrognosisProspective StudiesProto-OncogenesRemission InductionSurvival RateTranscription FactorsTranslocation, GeneticYoung Adult