Startseite BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia
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BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia

  • Margaritis Avgeris , Lamprini Stamati , Christos K. Kontos ORCID logo , Despina Piatopoulou , Antonios Marmarinos , Marieta Xagorari , Margarita Baka , Dimitrios Doganis , Theodora Anastasiou , Helen Kosmidis , Dimitrios Gourgiotis und Andreas Scorilas ORCID logo EMAIL logo
Veröffentlicht/Copyright: 17. Juli 2018
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 56 Heft 12

Abstract

Background

Risk-adjusted treatment has led to outstanding improvements of the remission and survival rates of childhood acute lymphoblastic leukemia (ALL). Nevertheless, overtreatment-related toxicity and resistance to therapy have not been fully prevented. In the present study, we evaluated for the first time the clinical impact of the apoptosis-related BCL2L12 gene in prognosis and risk stratification of BFM-treated childhood ALL.

Methods

Bone marrow specimens were obtained from childhood ALL patients upon disease diagnosis and the end-of-induction (EoI; day 33) of the BFM protocol, as well as from control children. Following total RNA extraction and reverse transcription, BCL2L12 expression levels were determined by qPCR. Patients’ cytogenetics, immunophenotyping and minimal residual disease (MRD) evaluation were performed according to the international guidelines.

Results

BCL2L12 expression was significantly increased in childhood ALL and correlated with higher BCL2/BAX expression ratio and favorable disease markers. More importantly, BCL2L12 expression was associated with disease remission, while the reduced BCL2L12 expression was able to predict patients’ poor response to BFM therapy, in terms of M2-M3 response and MRD≥0.1% on day 15. The survival analysis confirmed the significantly higher risk of the BFM-treated patients underexpressing BCL2L12 at disease diagnosis for early relapse and worse survival. Lastly, evaluation of BCL2L12 expression clearly strengthened the prognostic value of the established disease prognostic markers, leading to superior prediction of patients’ outcome and improved specificity of BFM risk stratification.

Conclusions

The expression levels of the apoptosis-related BCL2L12 predict response to treatment and survival outcome of childhood ALL patients receiving BFM chemotherapy.

Keywords: apoptosis; BCL2; BCL2-like 12; Berlin-Frankfurt-Münster; biomarker; cancer marker; childhood ALL; hematological cancer; pediatric cancer; tumor marker
Corresponding author: Prof. Andreas Scorilas, Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 157 01 Panepistimiopolis, Athens, Greece, Phone: +30-210-727-4306, Fax: +30-210-727-4158

Acknowledgments

We wish to sincerely thank Dr. M. Varvoutsi, Dr. A. Pourtsidis 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.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-0507).

Received: 2018-01-22
Accepted: 2018-06-07
Published Online: 2018-07-17
Published in Print: 2018-11-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

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  2. Editorial
  3. Observing an analyzer’s operational life cycle: a useful management tool for clinical laboratories
  4. Reviews
  5. Personalized laboratory medicine: a patient-centered future approach
  6. Circular RNAs: a new class of biomarkers as a rising interest in laboratory medicine
  7. Mini Review
  8. Impact of interactions between drugs and laboratory test results on diagnostic test interpretation – a systematic review
  9. Opinion Paper
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  12. Joint EFLM-COLABIOCLI Recommendation for venous blood sampling
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evidence for the positive impact of ISO 9001 and ISO 15189 quality systems on laboratory performance – evaluation of immunohaematology external quality assessment results during 19 years in Austria
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  18. Evaluation of serum alkaline phosphatase measurement through the 4-year trueness verification program in China
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  20. The clinical significance of borderline results of the Elia CTD Screen assay
  21. Reference Values and Biological Variations
  22. Reference intervals for 33 biochemical analytes in healthy Indian population: C-RIDL IFCC initiative
  23. Cancer Diagnostics
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  25. Cardiovascular Diseases
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  28. Impact of blood cell counts and volumes on glucose concentration in uncentrifuged serum and lithium-heparin blood tubes
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  36. Analytical and clinical validation of the new Roche Elecsys Vitamin D Total II assay
  37. Analytical validation of two second generation thyroglobulin immunoassays (Roche and Thermo Fisher)
  38. Omission of preservatives during 24-h of urine collection for the analysis of fractionated metanephrines enhance patient convenience
  39. Transient monoclonal gammopathy in a 2-year-old child with combined viral and bacterial infection
  40. Nephelometric assay of urine free light chains: an alternative and early clinical test for Bence-Jones protein quantification
  41. Congress Abstracts
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https://doi.org/10.1515/cclm-2018-0507
Schlagwörter für diesen Artikel
apoptosis; BCL2; BCL2-like 12; Berlin-Frankfurt-Münster; biomarker; cancer marker; childhood ALL; hematological cancer; pediatric cancer; tumor marker

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Observing an analyzer’s operational life cycle: a useful management tool for clinical laboratories
  4. Reviews
  5. Personalized laboratory medicine: a patient-centered future approach
  6. Circular RNAs: a new class of biomarkers as a rising interest in laboratory medicine
  7. Mini Review
  8. Impact of interactions between drugs and laboratory test results on diagnostic test interpretation – a systematic review
  9. Opinion Paper
  10. Uncertainty in measurement and total error: different roads to the same quality destination?
  11. Guidelines and Recommendations
  12. Joint EFLM-COLABIOCLI Recommendation for venous blood sampling
  13. General Clinical Chemistry and Laboratory Medicine
  14. Evidence for the positive impact of ISO 9001 and ISO 15189 quality systems on laboratory performance – evaluation of immunohaematology external quality assessment results during 19 years in Austria
  15. Effects of high-dose, intravenous lipid emulsion on laboratory tests in humans: a randomized, placebo-controlled, double-blind, clinical crossover trial
  16. Commutability of the certified reference materials for the standardization of β-amyloid 1-42 assay in human cerebrospinal fluid: lessons for tau and β-amyloid 1-40 measurements
  17. Failure rate prediction of equipment: can Weibull distribution be applied to automated hematology analyzers?
  18. Evaluation of serum alkaline phosphatase measurement through the 4-year trueness verification program in China
  19. Increased serum concentrations of soluble ST2 predict mortality after burn injury
  20. The clinical significance of borderline results of the Elia CTD Screen assay
  21. Reference Values and Biological Variations
  22. Reference intervals for 33 biochemical analytes in healthy Indian population: C-RIDL IFCC initiative
  23. Cancer Diagnostics
  24. BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia
  25. Cardiovascular Diseases
  26. The correlation between glucose fluctuation from self-monitored blood glucose and the major adverse cardiac events in diabetic patients with acute coronary syndrome during a 6-month follow-up by WeChat application
  27. Diabetes
  28. Impact of blood cell counts and volumes on glucose concentration in uncentrifuged serum and lithium-heparin blood tubes
  29. Letters to the Editor
  30. Standard process-oriented workflow introduces pre-analytical error when used in large study sample batches
  31. Comparison of three staining methods in the automated digital cell imaging analyzer Sysmex DI-60
  32. Detection of Plasmodium falciparum using automated digital cell morphology analyzer Sysmex DI-60
  33. Serum ischemia-modified albumin concentration may reflect long-term hypoxia in chronic respiratory disease: a pilot study
  34. Wet absorptive microsampling at home for HbA1c monitoring in diabetic children
  35. Serum endocan levels in patients with chronic obstructive pulmonary disease: a potential role in the evaluation of susceptibility to exacerbation
  36. Analytical and clinical validation of the new Roche Elecsys Vitamin D Total II assay
  37. Analytical validation of two second generation thyroglobulin immunoassays (Roche and Thermo Fisher)
  38. Omission of preservatives during 24-h of urine collection for the analysis of fractionated metanephrines enhance patient convenience
  39. Transient monoclonal gammopathy in a 2-year-old child with combined viral and bacterial infection
  40. Nephelometric assay of urine free light chains: an alternative and early clinical test for Bence-Jones protein quantification
  41. Congress Abstracts
  42. Congress of Laboratory Medicine and Clinical Chemistry 7th Annual Meeting of the Austrian Society for Laboratory Medicine and Clinical Chemistry (ÖGLMKC)
  43. 50th National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC – Laboratory Medicine)
  44. Revolution drives Evolution – from measuring to understanding: Annual meeting of Swiss Society of Clinical Chemistry (SSCC) in Bern, November 15-16 2018
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