Overexpression of BCL2 and BAX following BFM induction therapy predicts ch-ALL patients’ poor response to treatment and short-term relapse
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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.
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.
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.
In conclusion, BCL2 and BAX could be effectively used for an enhanced prediction of BFM-treated patients’ outcome.
KeywordsChildhood acute lymphoblastic leukemia (ch-ALL) Apoptosis Berlin–Frankfurt–Münster treatment protocol Chemotherapy resistance Molecular tumor markers
We wish to sincerely thank Dr. M. Varvoutsi, Dr. D. Bouhoutsou, Dr. A. Pourtsidis, Dr. D. Doganis and Dr. M. Servitzoglou for their valuable professional assistance in the characterization and collection of our samples. We would also like to thank the nursing staff of the Department of Pediatric Oncology, “P&A Kyriakou” Children’s Hospital for their expert help with the collection of samples. We are also very grateful to Dr. A. Kolialexi for her assistance during the karyotype analysis and to Dr. A. Marmarinos for his contribution in editing the paper.
Conflict of interest
The authors have to declare no conflict of interest (financial or non-financial).
The study was approved by the Ethics Committee of “P&A Kyriakou” Children’s Hospital, Athens, Greece, and performed with respect to the ethical standards of the Declaration of Helsinki, as revised in 2008.
Informed consent was obtained from parents and legal guardians of the participating patients.
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