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Journal of Cancer Research and Clinical Oncology

, Volume 133, Issue 11, pp 875–893 | Cite as

Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia

  • Jan StyczynskiEmail author
  • Mariusz Wysocki
  • Robert Debski
  • Krzysztof Czyzewski
  • Beata Kolodziej
  • Beata Rafinska
  • Malgorzata Kubicka
  • Sylwia Koltan
  • Andrzej Koltan
  • Monika Pogorzala
  • Andrzej Kurylak
  • Dorota Olszewska-Slonina
  • Walentyna Balwierz
  • Edyta Juraszewska
  • Maria Wieczorek
  • Igor Olejnik
  • Maryna Krawczuk-Rybak
  • Marta Kuzmicz
  • Jerzy Kowalczyk
  • Jolanta Stefaniak
  • Wanda Badowska
  • Danuta Sonta-Jakimczyk
  • Tomasz Szczepanski
  • Michal Matysiak
  • Iwona Malinowska
  • Elzbieta Stanczak
Original Paper

Abstract

Purpose

Cellular resistance in childhood acute leukemias might be related to profile and function of multidrug resistance proteins and apoptosis regulating proteins. The aims of the study were: (1) analysis of expression of MRP1, PGP1, LRP, BCL-2 and p53 proteins; (2) correlation with ex vivo drug resistance, and (3) analysis of their prognostic impact on clinical outcome in childhood acute lymphoblastic (ALL) and acute myeloid (AML) leukemia.

Methods

Total number of 787 children diagnosed for initial ALL (n = 527), relapsed ALL (n = 104), initial AML (n = 133) and relapsed AML (n = 23) were included into the study. Mean follow-up period was 3.5 years. Drug resistance for up to 30 anticancer agents was performed by the MTT assay. Expression of all proteins was tested by flow cytometry.

Results

Both initial AML and relapsed ALL samples showed higher drug resistance than initial ALL samples. No significant differences were found in drug resistance between initial and relapsed AML samples. The presence of multidrug resistance and apoptosis proteins had no impact on pDFS in iALL and iAML, however strong trend towards adverse prognostic impact of MRP1, PGP and LRP on pDFS in rALL was observed. The same trend was observed for each of analyzed co-expressions of tested multidrug resistance proteins.

Conclusions

The phenomenon of cellular drug resistance in childhood acute leukemias is multifactorial and plays an important role in response to therapy. Expression of MRP1, PGP and LRP proteins, as well as their co-expression play possible role in childhood relapsed ALL.

Keywords

Acute lymphoblastic leukemia Acute myelogenous leukemia Relapse PGP MRP1 LRP Drug resistance 

Notes

Acknowledgments

The authors thank the anonymous reviewers for their effort to improve quality of this paper. This study was supported by grants KBN 6 PO5E 082 21 and N407 078 32/2964.

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Jan Styczynski
    • 1
    Email author
  • Mariusz Wysocki
    • 1
  • Robert Debski
    • 1
  • Krzysztof Czyzewski
    • 1
  • Beata Kolodziej
    • 1
  • Beata Rafinska
    • 1
  • Malgorzata Kubicka
    • 1
  • Sylwia Koltan
    • 1
  • Andrzej Koltan
    • 1
  • Monika Pogorzala
    • 1
  • Andrzej Kurylak
    • 1
  • Dorota Olszewska-Slonina
    • 2
  • Walentyna Balwierz
    • 3
  • Edyta Juraszewska
    • 3
  • Maria Wieczorek
    • 4
  • Igor Olejnik
    • 4
  • Maryna Krawczuk-Rybak
    • 5
  • Marta Kuzmicz
    • 5
  • Jerzy Kowalczyk
    • 6
  • Jolanta Stefaniak
    • 6
  • Wanda Badowska
    • 7
  • Danuta Sonta-Jakimczyk
    • 8
  • Tomasz Szczepanski
    • 8
  • Michal Matysiak
    • 9
  • Iwona Malinowska
    • 9
  • Elzbieta Stanczak
    • 9
  1. 1.Department of Pediatric Hematology and Oncology, Collegium MedicumNicolaus Copernicus UniversityBydgoszczPoland
  2. 2.Department of Biology, Collegium MedicumNicolaus Copernicus UniversityBydgoszczPoland
  3. 3.Department of Pediatric Hematology and OncologyCMUJKrakowPoland
  4. 4.Department of Pediatric Hematology and OncologyPediatric CenterChorzowPoland
  5. 5.Department of Pediatric Hematology and OncologyMedical UniversityBialystokPoland
  6. 6.Department of Pediatric Hematology and OncologyMedical UniversityLublinPoland
  7. 7.Department of Pediatric Hematology and OncologyWSSDOlsztynPoland
  8. 8.Department of Pediatric Hematology and OncologyMedical UniversityZabrzePoland
  9. 9.Department of Pediatric Hematology and OncologyMedical UniversityWarszawaPoland

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