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Gene expression signatures and ex vivo drug sensitivity profiles in children with acute lymphoblastic leukemia

Journal of Applied Genetics volume 53, pages 83–91 (2012)Cite this article

Abstract

Introduction

Causes of treatment failure in acute lymphoblastic leukemia (ALL) are still poorly understood. Microarray technology gives new possibilities for the analysis of the biology of leukemias. We hypothesize that drug sensitivity in pediatric ALL is driven by specific molecular mechanisms that correlate with gene expression profiles assessed by microarray analysis.

Objective

The aim of the study was to determine the ex vivo resistance profiles of 20 antileukemic drugs and gene expression profiles, with relation to response to initial therapy.

Patients and methods

Lymphoblasts were analyzed after bone marrow biopsy was obtained from 56 patients. The profile of in vitro resistance to drugs was determined in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT) cytotoxicity assay. High-quality total RNA was prepared and hybridized to oligonucleotide arrays HG-U133A 2.0 Chip (Affymetrix). The expression of selected genes was tested by qualitative reverse transcription polymerase chain reaction (qRT-PCR).

Results and conclusions

The exposure of leukemic blasts to drugs initiates a complex cellular response, which reflects global changes in gene expression. Changes in the expression of several genes are highly correlated with drug resistance.

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Acknowledgments

This study was supported by Grant MNiSW No. N407 078 32/2964 and Grant UMK 10/2009.

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Affiliations

  1. Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

    Joanna Szczepanek, Monika Pogorzala, Mariusz Wysocki & Jan Styczynski

  2. Department of Plant Physiology and Biotechnology, Nicolaus Copernicus University, Torun, Poland

    Joanna Szczepanek & Andrzej Tretyn

  3. Department of Clinical and Experimental Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland

    Michal Jarzab

  4. Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Gliwice, Poland

    Malgorzata Oczko-Wojciechowska, Malgorzata Kowalska & Barbara Jarzab

  5. Department of Clinical Genetics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

    Olga Haus

  6. Department of Plant Physiology and Biotechnology, Nicolaus Copernicus University, ul. Gagarina 9, 87-100, Torun, Poland

    Joanna Szczepanek

Authors
  1. Joanna Szczepanek
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  2. Michal Jarzab
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  3. Malgorzata Oczko-Wojciechowska
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  4. Malgorzata Kowalska
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  6. Olga Haus
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  7. Monika Pogorzala
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  8. Mariusz Wysocki
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  9. Barbara Jarzab
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  10. Jan Styczynski
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Correspondence to Joanna Szczepanek.

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Szczepanek, J., Jarzab, M., Oczko-Wojciechowska, M. et al. Gene expression signatures and ex vivo drug sensitivity profiles in children with acute lymphoblastic leukemia. J Appl Genetics 53, 83–91 (2012). https://doi.org/10.1007/s13353-011-0073-x

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  • DOI: https://doi.org/10.1007/s13353-011-0073-x

Keywords

  • Acute leukemia
  • Children
  • Drug resistance
  • Gene expression profiles
  • Microarrays