PURPOSE: To validate ERG overexpression as an adverse predictor and assess its prognostic value in the context of other molecular markers in cytogenetically normal (CN) -acute myeloid leukemia (AML). PATIENTS AND METHODS: Seventy-six adult patients with primary CN-AML, younger than 60 years and treated on Cancer and Leukemia Group B (CALGB) trial 19808, were evaluated for ERG expression by quantitative reverse transcriptase polymerase chain reaction. They were then combined with 72 patients enrolled onto CALGB 9621 for analyses that included other molecular markers. RESULTS: Similar to patients enrolled onto CALGB 9621, high ERG expressers on CALGB 19808 had fewer complete remissions (CRs; P = .03) and worse event-free survival (EFS; P = .016) than low ERG expressers. In the combined set, high expressers (n = 55) had fewer CRs (P = .004) and shorter EFS (P < .001) than low expressers (n = 93). High ERG predicted failure to achieve CR (P = .004) after adjusting for BAALC expression (P = .04) and age (P = .008), and EFS (P = .004) after adjusting for FLT3 internal tandem duplication (ITD; P < .001). Among patients without FLT3-ITD (FLT3-ITD negative), only high ERG predicted shorter EFS (P = .001). Among NPM1-mutated (NPM1 positive) patients, high ERG predicted shorter EFS (P = .003), after adjusting for FLT3-ITD (P < .001). When all three markers were considered together, in the favorable FLT3-ITD-negative/NPM1-positive subset, high ERG was the only factor predicting shorter EFS (P = .002). CONCLUSION: We validated ERG overexpression as an adverse predictor in CN-AML. Moreover, by using ERG expression levels, we improved the previously proposed molecular-risk classification of CN-AML based on the presence or absence of FLT3-ITD and NPM1 mutations, given that we identified subsets with different outcome among FLT3-ITD-negative, NPM1-positive, and FLT3-ITD-negative/NPM1-positive patients.
PURPOSE: To validate ERG overexpression as an adverse predictor and assess its prognostic value in the context of other molecular markers in cytogenetically normal (CN) -acute myeloid leukemia (AML). PATIENTS AND METHODS: Seventy-six adult patients with primary CN-AML, younger than 60 years and treated on Cancer and Leukemia Group B (CALGB) trial 19808, were evaluated for ERG expression by quantitative reverse transcriptase polymerase chain reaction. They were then combined with 72 patients enrolled onto CALGB 9621 for analyses that included other molecular markers. RESULTS: Similar to patients enrolled onto CALGB 9621, high ERG expressers on CALGB 19808 had fewer complete remissions (CRs; P = .03) and worse event-free survival (EFS; P = .016) than low ERG expressers. In the combined set, high expressers (n = 55) had fewer CRs (P = .004) and shorter EFS (P < .001) than low expressers (n = 93). High ERG predicted failure to achieve CR (P = .004) after adjusting for BAALC expression (P = .04) and age (P = .008), and EFS (P = .004) after adjusting for FLT3 internal tandem duplication (ITD; P < .001). Among patients without FLT3-ITD (FLT3-ITD negative), only high ERG predicted shorter EFS (P = .001). Among NPM1-mutated (NPM1 positive) patients, high ERG predicted shorter EFS (P = .003), after adjusting for FLT3-ITD (P < .001). When all three markers were considered together, in the favorable FLT3-ITD-negative/NPM1-positive subset, high ERG was the only factor predicting shorter EFS (P = .002). CONCLUSION: We validated ERG overexpression as an adverse predictor in CN-AML. Moreover, by using ERG expression levels, we improved the previously proposed molecular-risk classification of CN-AML based on the presence or absence of FLT3-ITD and NPM1 mutations, given that we identified subsets with different outcome among FLT3-ITD-negative, NPM1-positive, and FLT3-ITD-negative/NPM1-positive patients.
Authors: Steven M Kornblau; Mark D Minden; David B Rosen; Santosh Putta; Aileen Cohen; Todd Covey; David C Spellmeyer; Wendy J Fantl; Urte Gayko; Alessandra Cesano Journal: Clin Cancer Res Date: 2010-06-04 Impact factor: 12.531
Authors: Sebastian Schwind; Kati Maharry; Michael D Radmacher; Krzysztof Mrózek; Kelsi B Holland; Dean Margeson; Susan P Whitman; Christopher Hickey; Heiko Becker; Klaus H Metzeler; Peter Paschka; Claudia D Baldus; Shujun Liu; Ramiro Garzon; Bayard L Powell; Jonathan E Kolitz; Andrew J Carroll; Michael A Caligiuri; Richard A Larson; Guido Marcucci; Clara D Bloomfield Journal: J Clin Oncol Date: 2010-11-15 Impact factor: 44.544
Authors: Björn Hackanson; Heiko Becker; Tobias Berg; Mascha Binder; Christine Dierks; Jesús Duque-Afonso; Michael D Lairmore; Henning S Schäfer; Marc Schnitzler; Robert Zeiser; Uwe Martens; Roland Mertelsmann; Michael Lübbert Journal: Cancer Res Date: 2008-07-15 Impact factor: 12.701
Authors: Guido Marcucci; Krzysztof Mrózek; Michael D Radmacher; Ramiro Garzon; Clara D Bloomfield Journal: Blood Date: 2010-11-02 Impact factor: 22.113
Authors: Guido Marcucci; Kati Maharry; Michael D Radmacher; Krzysztof Mrózek; Tamara Vukosavljevic; Peter Paschka; Susan P Whitman; Christian Langer; Claudia D Baldus; Chang-Gong Liu; Amy S Ruppert; Bayard L Powell; Andrew J Carroll; Michael A Caligiuri; Jonathan E Kolitz; Richard A Larson; Clara D Bloomfield Journal: J Clin Oncol Date: 2008-09-22 Impact factor: 44.544