title: Overexpression of BCL2 and BAX following BFM induction therapy predicts ch-ALL patients' poor response to treatment and short-term relapse.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Lamprini
authors.initials: L
authors.lastname: Stamati
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 157 01, Athens, Greece.
authors.forename: Margaritis
authors.initials: M
authors.lastname: Avgeris
authors.affiliation: Department of Pediatric Oncology, "P&A Kyriakou" Children's Hospital, Thivon & Levadias Str., 115 27, Athens, Greece.
authors.forename: Helen
authors.initials: H
authors.lastname: Kosmidis
authors.affiliation: Department of Pediatric Oncology, "P&A Kyriakou" Children's Hospital, Thivon & Levadias Str., 115 27, Athens, Greece.
authors.forename: Margarita
authors.initials: M
authors.lastname: Baka
authors.affiliation: Laboratory of Hematology, "P&A Kyriakou" Children's Hospital, Thivon & Levadias Str., 115 27, Athens, Greece.
authors.forename: Theodora
authors.initials: T
authors.lastname: Anastasiou
authors.affiliation: 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.
authors.forename: Despina
authors.initials: D
authors.lastname: Piatopoulou
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 157 01, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: 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.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Gourgiotis
mesh_terms: D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D007223:Infant; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D011241:Prednisone / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation; D014750:Vincristine / Q000627:therapeutic use; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C000595707:BCL2 protein, human; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D014750:Vincristine; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin
keywords: Apoptosis; Berlin–Frankfurt–Münster treatment protocol; Chemotherapy resistance; Childhood acute lymphoblastic leukemia (ch-ALL); Molecular tumor markers