1066PD - Overexpression of enhancer of zeste homolog 2 is associated with clinical outcome in acute myeloid leukemia patients

Date 01 October 2012
Event ESMO Congress 2012
Session Hematological malignancies
Topics Leukaemia
Translational Research
Presenter Po-Han Lin
Authors P. Lin1, S. Yeh2, L. Bai2, C. Lin2, C. Chiu2
  • 1Department Of Medical Genetics, China Medical University Hospital, 404 - Taichung city/TW
  • 2Internal Medicine, Division Of Hematology/oncology, China Medical University Hospital, 404 - taichung/TW

Abstract

Background

Enhancer of zeste homolog 2 (EZH2), a subunit of polycomb repressive complex 2 functioned as methyltransferase causing trimethylation at lysine-27 of histone 3, is involved in stem cell regulation and various cancers. It was reported two faces that both increased expression and mutation/deletion were implicated in cancer development and progression of different malignancies. For acute myeloid leukemia (AML), the clinical significance of EZH2 was not explored. In this study, we examined EZH2 expression and mutation and evaluated the association between EZH2 and patient survival.

Methods

A total of 105 patients, who were newly diagnosed as de novo AML and received intensive chemotherapy between 2004 January and 2010 December, were retrospectively analyzed. All patients received French-American-British (FAB) classification, karyotype analyses, immunophenotyping, detection of NPM mutation and FLT3 internal tandem duplication (FLT3/ITD). The mutation of EZH2 was identified by direct sequencing. An immunohistochemical analysis of EZH2 was performed on bone marrow biopsy samples, and overexpression was defined as more than 50% positive staining among the leukemic marrow.

Results

EZH2 overexpression was identified in 57 patients (54.3%), and no associated with age, gender, FAB classification, karyotype, FLT3/ITD and NPM mutation. Only two mutations were detected in this cohort. Patients with EZH2 overexpression had a significant shorter median overall survival (OS; 18.5 vs 40.7 months, p = 0.047) as well as a higher trend of relapsed/refractory disease (47.9% vs 66.7%, p = 0.052). Karyotype and FLT3/ITD were also the significant prognostic factors for the entire cohort and NPM mutation was a trend of favorable prognostic factor in intermediate-karyotype patients by univariate analysis. We defined a prognostic classification based on these four factors that was able to classify patients into four risk groups showing significant different survivals (median OS: not reached, not reached, 22.0 and 10.6 months, respectively; p < .0001) and probabilities of disease relapsed/refractory (p = 0.048).

Conclusion

EZH2 overexpression is a novel poor prognostic biomarker in AML patients. The current result indicated that EZH2 expression status may be incorporated into prognostic classification.

Disclosure

All authors have declared no conflicts of interest.