miR-125b predicts childhood acute lymphoblastic leukaemia poor response to BFM chemotherapy treatment

• Published in: British journal of cancer 2017-09, Vol.117 (6), p.801-812
• Main Authors: Piatopoulou, Despina, Avgeris, Margaritis, Marmarinos, Antonios, Xagorari, Marieta, Baka, Margarita, Doganis, Dimitrios, Kossiva, Lydia, Scorilas, Andreas, Gourgiotis, Dimitrios
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 631/67/1857; 631/67/1990/283/2125; 692/4017; 692/53/2422; Acute lymphoblastic leukemia; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Asparaginase - administration & dosage; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Bone marrow; Bone Marrow - pathology; Cancer Research; Chemotherapy; Child; Child, Preschool; Childhood; Children; Cytogenetics; Daunorubicin - administration & dosage; Disease Progression; DNA, Complementary; Down-Regulation; Drug Resistance; Drug Resistance, Neoplasm; Epidemiology; Female; Health risks; Humans; Infant; Kaplan-Meier Estimate; Leukemia; Male; Medical prognosis; MicroRNAs - analysis; MicroRNAs - metabolism; Molecular Medicine; Oncology; Polyadenylation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Prednisone - administration & dosage; Prognosis; Real-Time Polymerase Chain Reaction; Regression Analysis; Ribonucleic acid; RNA; Survival; Translational Therapeutics; Treatment Outcome; Vincristine - administration & dosage
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2017.256

Background: Despite the favourable survival rates of childhood acute lymphoblastic leukaemia (ALL), a significant number of patients present resistance to antileukaemic agents and dismal prognosis. In this study, we analysed miR-125b expression in childhood ALL and evaluated its clinical utility for patients treated with Berlin–Frankfurt–Münster (BFM) protocol. Methods: The study included 272 bone marrow specimens obtained on diagnosis and on BFM day 33 from 125 patients and 64 healthy children. Following extraction, RNA was polyadenylated and reverse transcribed. miR-125b levels were quantified by quantitative PCR. Cytogenetics, immunohistotype and MRD were analysed according to international guidelines. Results: Downregulated miR-125b levels were detected in childhood ALL patients and correlated with adverse prognosis. Following BFM induction, miR-125b levels were significantly increased, however, elevated day 33/diagnosis miR-125b ratio was associated with unfavourable disease features. Loss of miR-125b during diagnosis and higher day 33/diagnosis ratio were correlated with stronger risk for disease short-term relapse and patients’ worse survival. Moreover, multivariate regression models highlighted the independent prognostic value of miR-125b for childhood ALL. Finally, the combination of miR-125b with clinically used disease markers clearly enhanced the prediction of patients’ resistance to BFM chemotherapy. Conclusions: miR-125b significantly improves the prognosis of childhood ALL patients’ outcome under BFM treatment.