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Over expression of brain and acute leukemia,cytoplasmic and ETS-related gene is associated with poor outcome in acute myeloid leukemia
Authors:Syed Khizer Hasan  Nikhil V Patkar  Deepan Rajamanickam  Anant Gokarn  Antonio R Lucena-Araujo  Prashant Tembhare  Bhausaheb Bagal  Pratibha Kadam Amare  Hasmukh Jain  Sumeet Gujral  Manju Sengar  Papagudi Ganesan Subramanian  Navin Khattry
Institution:1. Cell and Tumor Biology Group, ACTREC, Tata Memorial Centre, Navi Mumbai, India;2. Hematopathology Laboratory, ACTREC, Tata Memorial Centre, Navi Mumbai, India;3. Department of Medical Oncology, Adult Hematolymphoid Disease Management Group, Tata Memorial Centre, Mumbai, India;4. Department of Genetics, Federal University of Pernambuco, Recife, Brazil;5. Laboratory of Cytogenetics, Tata Memorial Centre, Mumbai, India
Abstract:The high expression of brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) has been reported to influence the outcome in acute myeloid leukemia (AML), but due to limited prospective studies, their role as prognostic factors is unclear. At diagnosis, the prognostic value of BAALC and ERG expression with respect to other cytogenetic and molecular markers was analyzed in 149 AML patients. Patients were divided into quartiles which resulted in the formation of four groups (G1–G4) based on expression values of BAALC and ERG and clinical response defined across groups. Groups with similar survival probabilities were merged together and categorized subsequently as high versus low expressers. Patients with high BAALC and ERG expression had significantly lower overall survival (OS; BAALC: p = 0.001 at 5 years 29.4% vs. 69.8%; ERG: p < 0.0001 at 5 years 4% vs. 50.4%) and disease-free survival (BAALC: p = 0.001 at 5 years 19.5% vs. 69.8%; ERG: p < 0.0001 at 5 years 4.2% vs. 47%). Patients were further stratified combining BAALC and ERG expression in an integrative prognostic risk score (IPRS). After a median follow-up of 54 months (95% CI 45–63 months) among survivors, IPRS for high versus low expressers was a significant predictor for OS (BAALC + ERG: 4% vs. 71.6%, p < 0.0001) and DFS (BAALC + ERG: 4.5% vs. 74.1%, p < 0.0001). In a multivariate model, IPRS of BAALC + ERG expression retained prognostic significance for OS (hazard ratio HR] 2.96, 95%CI 1.91–4.59, p < 0.001) and DFS (HR 3.61, 95%CI 2.26–5.76, p < 0.001).
Keywords:AML  BAALC  ERG  prognostic markers  survival outcome
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