Overexpression of BCL2 and BAX following BFM induction therapy predicts ch-ALL patients’ poor response to treatment and short-term relapse - Journal of Cancer Research and Clinical Oncology

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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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).

Ethical standard

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

Informed consent was obtained from parents and legal guardians of the participating patients.

Authors and Affiliations

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

   Lamprini Stamati, Despina Piatopoulou & Dimitrios Gourgiotis

2. Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 157 01, Athens, Greece

   Margaritis Avgeris & Andreas Scorilas

3. Department of Pediatric Oncology, “P&A Kyriakou” Children’s Hospital, Thivon & Levadias Str., 115 27, Athens, Greece

   Helen Kosmidis & Margarita Baka

4. Laboratory of Hematology, “P&A Kyriakou” Children’s Hospital, Thivon & Levadias Str., 115 27, Athens, Greece

   Theodora Anastasiou

Corresponding author

Correspondence to Dimitrios Gourgiotis.