Lamprini Stamati1, Margaritis Avgeris2, Helen Kosmidis3, Margarita Baka3, Theodora Anastasiou4, Despina Piatopoulou1, Andreas Scorilas2, Dimitrios Gourgiotis5. 1. Laboratory of Clinical Biochemistry - Molecular Diagnostics, Second Department of Pediatrics, University of Athens Medical School, "P&A Kyriakou" Children's Hospital, Levadias 13 Str., 115 27, Athens, Greece. 2. Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 157 01, Athens, Greece. 3. Department of Pediatric Oncology, "P&A Kyriakou" Children's Hospital, Thivon & Levadias Str., 115 27, Athens, Greece. 4. Laboratory of Hematology, "P&A Kyriakou" Children's Hospital, Thivon & Levadias Str., 115 27, Athens, Greece. 5. Laboratory of Clinical Biochemistry - Molecular Diagnostics, Second Department of Pediatrics, University of Athens Medical School, "P&A Kyriakou" Children's Hospital, Levadias 13 Str., 115 27, Athens, Greece. dgourg@med.uoa.gr.
Abstract
PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL) patients who are at a higher risk of chemotherapy resistance and relapse is essential for successful treatment decisions, despite the application of novel therapies. The aim of the study is the evaluation of BCL2 and BAX expression for the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Münster (BFM) backbone protocol. METHODS: Bone marrow specimens were obtained at the time of diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL patients, as well as from 63 healthy children. Following extraction, total RNA was reverse transcribed and BCL2 and BAX expression levels were determined by qPCR. RESULTS: BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch-ALL compared to healthy children and were correlated with favorable prognostic disease features. Increased levels of BCL2 and BAX expression were associated with disease remission, as ch-ALL patients with lower expression ran a significantly higher risk of M2-M3 response, positive MRD and poor survival outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment induction was shown to represent an independent predictor of patients' short-term relapse, which was further confirmed in ch-ALL patients with favorable prognostic markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients' outcome.
PURPOSE: The identification of childhood acute lymphoblastic leukemia (ch-ALL) patients who are at a higher risk of chemotherapy resistance and relapse is essential for successful treatment decisions, despite the application of novel therapies. The aim of the study is the evaluation of BCL2 and BAX expression for the prognosis of ch-ALL patients treated with Berlin-Frankfurt-Münster (BFM) backbone protocol. METHODS: Bone marrow specimens were obtained at the time of diagnosis and on day 33 following BFM treatment induction from 82 ch-ALL patients, as well as from 63 healthy children. Following extraction, total RNA was reverse transcribed and BCL2 and BAX expression levels were determined by qPCR. RESULTS:BCL2 expression and BCL2/BAX ratio were strongly upregulated in ch-ALL compared to healthy children and were correlated with favorable prognostic disease features. Increased levels of BCL2 and BAX expression were associated with disease remission, as ch-ALL patients with lower expression ran a significantly higher risk of M2-M3 response, positive MRD and poor survival outcome. Moreover, the upregulation of BCL2 and BAX following BFM treatment induction was shown to represent an independent predictor of patients' short-term relapse, which was further confirmed in ch-ALL patients with favorable prognostic markers. CONCLUSIONS: In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients' outcome.
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