Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 22 August 2007

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Arico M, Valsecchi MG, Camitta B, Schrappe M, Chessells J, Baruchel A, Gaynon P, Silverman L, Janka-Schaub G, Kamps W, Pui CH, Masera G (2000) Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia. N Engl J Med 342:998–1006

    Article  PubMed  CAS  Google Scholar 

  • Borowitz MJ, Pullen DJ, Shuster JJ, Viswanatha D, Montgomery K, Willman CL, Camitta B (2003) Minimal residual disease detection in childhood precursor-B-cell acute lymphoblastic leukemia: relation to other risk factors. A Children’s Oncology Group study. Leukemia 17:1566–1572

    Article  PubMed  CAS  Google Scholar 

  • Den Boer ML, Pieters R, Kazemier KM, Rottier MM, Zwaan CM, Kaspers GJ, Janka-Schaub G, Henze G, Creutzig U, Scheper RJ, Veerman AJ (1998) Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. Blood 91:2092–2098

    Google Scholar 

  • Den Boer ML, Kapaun P, Pieters R, Kazemier KM, Janka-Schaub GE, Veerman AJ (1999a) Myeloid antigen co-expression in childhood acute lymphoblastic leukaemia: relationship with in vitro drug resistance. Br J Haematol 105:876–882

    Article  Google Scholar 

  • Den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Creutzig U, Kaspers GJ, Kearns PR, Hall AG, Pearson AD, Veerman AJ (1999b) Different expression of glutathione S-transferase alpha, mu and pi in childhood acute lymphoblastic and myeloid leukaemia. Br J Haematol 104:321–327

    Article  Google Scholar 

  • Den Boer ML, Pieters R, Kazemier KM, Janka-Schaub GE, Henze G, Veerman AJ (1999c) Relationship between the intracellular daunorubicin concentration, expression of major vault protein/lung resistance protein and resistance to anthracyclines in childhood acute lymphoblastic leukemia. Leukemia 13:2023–2030

    Article  Google Scholar 

  • Den Boer ML, Harms DO, Pieters R, Kazemier KM, Gobel U, Korholz D, Graubner U, Haas RJ, Jorch N, Spaar HJ, Kaspers GJ, Kamps WA, Van der Does-Van den Berg A, Van Wering ER, Veerman AJ, Janka-Schaub GE (2003) Patient stratification based on prednisolone-vincristine-asparaginase resistance profiles in children with acute lymphoblastic leukemia. J Clin Oncol 21:3262–3268

    Article  CAS  Google Scholar 

  • Dluzniewska A, Balwierz W, Armata J, Balcerska A, Chybicka A, Kowalczyk J, Matysiak M, Ochocka M, Radwanska U, Rokicka-Milewska R, Sonta-Jakimczyk D, Wachowiak J, Wysocki M (2005) Twenty years of Polish experience with three consecutive protocols for treatment of childhood acute myelogenous leukemia. Leukemia 19:2117–2124

    Article  PubMed  CAS  Google Scholar 

  • Einsiedel HG, von Stackelberg A, Hartmann R, Fengler R, Schrappe M, Janka-Schaub G, Mann G, Hahlen K, Gobel U, Klingebiel T, Ludwig WD, Henze G (2005) Long-term outcome in children with relapsed ALL by risk-stratified salvage therapy: results of trial acute lymphoblastic leukemia-relapse study of the Berlin-Frankfurt-Munster Group 87. J Clin Oncol 23:7942–7950

    Article  PubMed  Google Scholar 

  • Fleischhack G, Hasan C, Graf N, Mann G, Bode U (1998) IDA-FLAG (idarubicin, fludarabine, cytarabine, G-CSF), an effective remission-induction therapy for poor-prognosis AML of childhood prior to allogeneic or autologous bone marrow transplantation: experiences of a phase II trial. Br J Haematol 102:647–655

    Article  PubMed  CAS  Google Scholar 

  • Funato T, Harigae H, Abe S, Sasaki T (2004) Assessment of drug resistance in acute myeloid leukemia. Expert Rev Mol Diagn 4:705–713

    Article  PubMed  CAS  Google Scholar 

  • Ikeda K, Oka M, Yamada Y, Soda H, Fukuda M, Kinoshita A, Tsukamoto K, Noguchi Y, Isomoto H, Takeshima F, Murase K, Kamihira S, Tomonaga M, Kohno S (1999) Adult T-cell leukemia cells over-express the multidrug-resistance-protein (MRP) and lung-resistance-protein (LRP) genes. Int J Cancer 82:599–604

    Article  PubMed  CAS  Google Scholar 

  • Kakihara T, Tanaka A, Watanabe A, Yamamoto K, Kanto K, Kataoka S, Ogawa A, Asami K, Uchiyama M (1999) Expression of multidrug resistance-related genes does not contribute to risk factors in newly diagnosed childhood acute lymphoblastic leukemia. Pediatr Int 41:641–647

    PubMed  CAS  Google Scholar 

  • Kardos G, Zwaan CM, Kaspers GJ, de-Graaf SS, de Bont ES, Postma A, Bokkerink JP, Weening RS, van der Does-van den Berg A, van Wering ER, Korbijn C, Hahlen K (2005) Treatment strategy and results in children treated on three Dutch Childhood Oncology Group acute myeloid leukemia trials. Leukemia 19:2063–2071

    Article  PubMed  CAS  Google Scholar 

  • Kasimir-Bauer S, Ottinger H, Meusers P, Beelen DW, Brittinger G, Seeber S, Scheulen ME (1998) In acute myeloid leukemia, coexpression of at least two proteins, including P-glycoprotein, the multidrug resistance-related protein, bcl-2, mutant p53, and heat-shock protein 27, is predictive of the response to induction chemotherapy. Exp Hematol 26:1111–1117

    PubMed  CAS  Google Scholar 

  • Kasimir-Bauer S, Beelen D, Flasshove M, Noppeney R, Seeber S, Scheulen ME (2002) Impact of the expression of P glycoprotein, the multidrug resistance-related protein, bcl-2, mutant p53, and heat shock protein 27 on response to induction therapy and long-term survival in patients with de novo acute myeloid leukemia. Exp Hematol 30:1302–1308

    Article  PubMed  CAS  Google Scholar 

  • Kaspers GJ, Creutzig U (2005) Pediatric acute myeloid leukemia: international progress and future directions. Leukemia 19:2025–2029

    Article  PubMed  CAS  Google Scholar 

  • Kaspers GJ, Kardos G, Pieters R, Van Zantwijk CH, Klumper E, Hahlen K, de Waal FC, van Wering ER, Veerman AJ (1994a) Different cellular drug resistance profiles in childhood lymphoblastic and non-lymphoblastic leukemia: a preliminary report. Leukemia 8:1224–1229

    PubMed  CAS  Google Scholar 

  • Kaspers GJ, Pieters R, Klumper E, De Waal FC, Veerman AJ (1994b) Glucocorticoid resistance in childhood leukemia. Leuk Lymphoma 13:187–201

    PubMed  CAS  Google Scholar 

  • Kaspers GJ, Veerman AJ, Pieters R, Van Zantwijk CH, Smets LA, Van Wering ER, Van Der Does-Van Den Berg A (1997) In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 90:2723–2729

    PubMed  CAS  Google Scholar 

  • Klumper E, Pieters R, Kaspers GJ, Huismans DR, Loonen AH, Rottier MM, van Wering ER, van der Does-van den Berg A, Hahlen K, Creutzig U, Veerman AJ (1995a) In vitro chemosensitivity assessed with the MTT assay in childhood acute non-lymphoblastic leukemia. Leukemia 9:1864–1869

    PubMed  CAS  Google Scholar 

  • Klumper E, Pieters R, Veerman AJ, Huismans DR, Loonen AH, Hahlen K, Kaspers GJ, van Wering ER, Hartmann R, Henze G (1995b) In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia. Blood 86:3861–3868

    PubMed  CAS  Google Scholar 

  • Kofler R, Schmidt S, Kofler A, Ausserlechner MJ (2003) Resistance to glucocorticoid-induced apoptosis in lymphoblastic leukemia. J Endocrinol 178:19–27

    Article  PubMed  CAS  Google Scholar 

  • Moricke A, Zimmermann M, Reiter A, Gadner H, Odenwald E, Harbott J, Ludwig WD, Riehm H, Schrappe M (2005) Prognostic impact of age in children and adolescents with acute lymphoblastic leukemia: data from the trials ALL-BFM 86, 90, and 95. Klin Padiatr 217:310–320

    Article  PubMed  CAS  Google Scholar 

  • Ogretmen B, Barredo JC (2000) Safa AR: Increased expression of lung resistance-related protein and multidrug resistance-associated protein messenger RNA in childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol 22:45–49

    Article  PubMed  CAS  Google Scholar 

  • Ohno N, Tani A, Chen ZS, Uozumi K, Hanada S, Akiba S, Ren XQ, Furukawa T, Sumizawa T, Arima T, Akiyama SI (2001) Prognostic significance of multidrug resistance protein in adult T-cell leukemia. Clin Cancer Res 7:3120–3126

    PubMed  CAS  Google Scholar 

  • Plasschaert S, Vellenga E, De Bont E, Van der Kolk D, Veerman A, Sluiter W, Daenen S, De Vries E, Kamps WA (2003) High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children. Leuk Lymphoma 44:85–95

    Article  PubMed  CAS  Google Scholar 

  • Plasschaert SL, de Bont ES, Boezen M, vander Kolk DM, Daenen SM, Faber KN, Kamps WA, de Vries EG, Vellenga E (2005) Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia. Clin Cancer Res 11:8661–8668

    Article  PubMed  CAS  Google Scholar 

  • Pui CH, Crist WM (1995) Treatment of childhood leukemias. Curr Opin Oncol 7:36–44

    PubMed  CAS  Google Scholar 

  • Pui CH, Evans WE 2006) Treatment of acute lymphoblastic leukemia. N Engl J Med 354:166–178

    Article  PubMed  CAS  Google Scholar 

  • Ramakers-van Woerden NL, Pieters R, Hoelzer D, Slater RM, den Boer ML, Loonen AH, Harbott J, Janka-Schaub GE, Ludwig WD, Ossenkoppele GJ, van Wering ER, Veerman AJ (2002) In vitro drug resistance profile of Philadelphia positive acute lymphoblastic leukemia is heterogeneous and related to age: a report of the Dutch and German Leukemia Study Groups. Med Pediatr Oncol 38:379–386

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro RC, Razzouk BI, Pounds S, Hijiya N, Pui CH, Rubnitz JE (2005) Successive clinical trials for childhood acute myeloid leukemia at St Jude Children’s Research Hospital, from 1980 to 2000. Leukemia 19:2125–2129

    Article  PubMed  CAS  Google Scholar 

  • Riehm H, Reiter A, Schrappe M, Berthold F, Dopfer R, Gerein V, Ludwig R, Ritter J, Stollmann B, Henze G (1987) Corticosteroid-dependent reduction of leukocyte count in blood as a prognostic factor in acute lymphoblastic leukemia in childhood (therapy study ALL-BFM 83). Klin Padiatr 199:151–160

    Article  PubMed  CAS  Google Scholar 

  • Sauerbrey A, Voigt A, Wittig S, Hafer R, Zintl F (2000) Messenger RNA analysis of the multidrug resistance related protein (MRP1) and the lung resistance protein (LRP) in de novo and relapsed childhood acute lymphoblastic leukemia. Leuk Lymphoma 43:875–879

    Article  CAS  Google Scholar 

  • Schrappe M, Reiter A, Ludwig WD, Harbott J, Zimmermann M, Hiddemann W, Niemeyer C, Henze G, Feldges A, Zintl F, Kornhuber B, Ritter J, Welte K, Gadner H, Riehm H (2000a) Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group. Blood 95:3310–3322

    PubMed  CAS  Google Scholar 

  • Schrappe M, Reiter A, Zimmermann M, Harbott J, Ludwig WD, Henze G, Gadner H, Odenwald E, Riehm H (2000b) Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia 14:2205–2222

    Article  PubMed  CAS  Google Scholar 

  • Steinbach D, Lengemann J, Voigt A, Hermann J, Zintl F, Sauerbrey A (2003a) Response to chemotherapy and expression of the genes encoding the multidrug resistance-associated proteins MRP2, MRP3, MRP4, MRP5, and SMRP in childhood acute myeloid leukemia. Clin Cancer Res 9:1083–1086

    PubMed  CAS  Google Scholar 

  • Steinbach D, Wittig S, Cario G, Viehmann S, Mueller A, Gruhn B, Haefer R, Zintl F, Sauerbrey A (2003b) The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype. Blood 102:4493–4498

    Article  PubMed  CAS  Google Scholar 

  • Styczynski J, Wysocki M (2004a) Ex vivo drug resistance in childhood acute myeloid leukemia on relapse is not higher than at first diagnosis. Pediatr Blood Cancer 42:195–199

    Article  PubMed  Google Scholar 

  • Styczynski J, Wysocki M (2004b) Is the in vitro drug resistance profile the strongest prognostic factor in childhood acute lymphoblastic leukemia? J Clin Oncol 22:963–964

    Article  PubMed  Google Scholar 

  • Styczynski J, Wysocki M, Debski R, Juraszewska E, Malinowska I, Stanczak E, Ploszynska A, Stefaniak J, Mazur B, Szczepanski T (2002) Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia. Leuk Lymphoma 43:1843–1848

    Article  PubMed  CAS  Google Scholar 

  • Styczynski J, Kurylak A, Wysocki M (2005) Cytotoxicity of cortivazol in childhood acute lymphoblastic leukemia. Anticancer Res 25:2253–2258

    PubMed  CAS  Google Scholar 

  • Valera ET, Scrideli CA, Queiroz RG, Mori BM, Tone LG (2004) Multiple drug resistance protein (MDR-1), multidrug resistance-related protein (MRP) and lung resistance protein (LRP) gene expression in childhood acute lymphoblastic leukemia. Sao Paulo Med J 122:166–171

    Article  PubMed  Google Scholar 

  • van den Heuvel-Eibrink MM, Sonneveld P, Pieters R (2000) The prognostic significance of membrane transport-associated multidrug resistance (MDR) proteins in leukemia. Int J Clin Pharmacol Ther 38:94–110

    PubMed  Google Scholar 

  • van Dongen JJ, Seriu T, Panzer-Grumayer ER, Biondi A, Pongers-Willemse MJ, Corral L, Stolz F, Schrappe M, Masera G, Kamps WA, Gadner H, van Wering ER, Ludwig WD, Basso G, de Bruijn MA, Cazzaniga G, Hettinger K, van der Does-van den Berg A, Hop WC, Riehm H, Bartram CR (1998) Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood. Lancet 352:1731–1738

    Article  PubMed  Google Scholar 

  • Wysocki M, Styczynski J, Debski R, Kubicka M, Balwierz W, Juraszewska E, Rokicka-Milewska R, Malinowska I, Matysiak M, Stanczak E, Balcerska A, Ploszynska A, Kowalczyk JR, Stefaniak J, Malek U, Wachowiak J, Mazur B, Sonta-Jakimczyk D, Szczepanski T, Chybicka A, Ras M (2002) Drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse with respect to percentile values. Report of Polish Pediatric Leukemia and Lymphoma Study Group. Acta Haematol Pol 33:341–350

    Google Scholar 

  • Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR (2002) Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell 1:133–143

    Article  PubMed  CAS  Google Scholar 

  • Zhang JB, Sun Y, Dong J, Liu LX, Ning F (2005) [Expression of lung resistance protein and multidrug resistance-associated protein in naive childhood acute leukemia and their clinical significance]. Ai Zheng 24:1015–1017

    PubMed  CAS  Google Scholar 

  • Zhao Y, Yu L, Lou F, Wang Q, Pu J, Zhou Q (1999) [The clinical significance of lung resistance-related protein gene (lrp), multidrug resistance-associated protein gene (mrp) and mdr-1/p170 expression in acute leukemia]. Zhonghua Nei Ke Za Zhi38:760–763

    Google Scholar 

  • Zhao Y, Yu L, Wang Q, Lou F, Pu J (2002) [The relationship between expression of lung resistance-related protein gene or multidrug resistance-associated protein gene and prognosis in newly diagnosed acute leukemia]. Zhonghua Nei Ke Za Zhi 41:183–185

    PubMed  CAS  Google Scholar 

  • Zwaan CM (2003) Prognostic factors in AML. In: Toward subgroup-directed therapy in acute myeloid leukemia, Vrije Univeristeit. Amsterdam, pp 24–26

  • Zwaan CM, Kaspers GJ (2004) Possibilities for tailored and targeted therapy in paediatric acute myeloid leukaemia. Br J Haematol 127:264–279

    Article  PubMed  CAS  Google Scholar 

  • Zwaan CM, Kaspers GJ, Pieters R, Ramakers-Van Woerden NL, den Boer ML, Wunsche R, Rottier MM, Hahlen K, van Wering ER, Janka-Schaub GE, Creutzig U, Veerman AJ (2000) Cellular drug resistance profiles in childhood acute myeloid leukemia: differences between FAB types and comparison with acute lymphoblastic leukemia. Blood 96:2879–2886

    PubMed  CAS  Google Scholar 

  • Zwaan CM, Kaspers GJ, Pieters R, Hahlen K, Huismans DR, Zimmermann M, Harbott J, Slater RM, Creutzig U, Veerman AJ (2002) Cellular drug resistance in childhood acute myeloid leukemia is related to chromosomal abnormalities. Blood 100:3352–3360

    Article  PubMed  CAS  Google Scholar 

  • Zwaan CM, Meshinchi S, Radich JP, Veerman AJ, Huismans DR, Munske L, Podleschny M, Hahlen K, Pieters R, Zimmermann M, Reinhardt D, Harbott J, Creutzig U, Kaspers GJ, Griesinger F (2003) FLT3 internal tandem duplication in 234 children with acute myeloid leukemia: prognostic significance and relation to cellular drug resistance. Blood 102:2387–2394

    Article  PubMed  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, ul. Curie-Sklodowskiej 9, 85-094, Bydgoszcz, Poland

    Jan Styczynski, Mariusz Wysocki, Robert Debski, Krzysztof Czyzewski, Beata Kolodziej, Beata Rafinska, Malgorzata Kubicka, Sylwia Koltan, Andrzej Koltan, Monika Pogorzala & Andrzej Kurylak

  2. Department of Biology, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

    Dorota Olszewska-Slonina

  3. Department of Pediatric Hematology and Oncology, CMUJ, Krakow, Poland

    Walentyna Balwierz & Edyta Juraszewska

  4. Department of Pediatric Hematology and Oncology, Pediatric Center, Chorzow, Poland

    Maria Wieczorek & Igor Olejnik

  5. Department of Pediatric Hematology and Oncology, Medical University, Bialystok, Poland

    Maryna Krawczuk-Rybak & Marta Kuzmicz

  6. Department of Pediatric Hematology and Oncology, Medical University, Lublin, Poland

    Jerzy Kowalczyk & Jolanta Stefaniak

  7. Department of Pediatric Hematology and Oncology, WSSD, Olsztyn, Poland

    Wanda Badowska

  8. Department of Pediatric Hematology and Oncology, Medical University, Zabrze, Poland

    Danuta Sonta-Jakimczyk & Tomasz Szczepanski

  9. Department of Pediatric Hematology and Oncology, Medical University, Warszawa, Poland

    Michal Matysiak, Iwona Malinowska & Elzbieta Stanczak

Authors
  1. Jan Styczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariusz Wysocki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Debski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Krzysztof Czyzewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Beata Kolodziej
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Beata Rafinska
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Malgorzata Kubicka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sylwia Koltan
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Andrzej Koltan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Monika Pogorzala
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Andrzej Kurylak
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Dorota Olszewska-Slonina
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Walentyna Balwierz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Edyta Juraszewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Maria Wieczorek
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Igor Olejnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Maryna Krawczuk-Rybak
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Marta Kuzmicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Jerzy Kowalczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Jolanta Stefaniak
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Wanda Badowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Danuta Sonta-Jakimczyk
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Tomasz Szczepanski
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Michal Matysiak
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Iwona Malinowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Elzbieta Stanczak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jan Styczynski.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00432-007-0299-5

Rights and permissions

Reprints and permissions

About this article

Cite this article

Styczynski, J., Wysocki, M., Debski, R. et al. Predictive value of multidrug resistance proteins and cellular drug resistance in childhood relapsed acute lymphoblastic leukemia. J Cancer Res Clin Oncol 133, 875–893 (2007). https://doi.org/10.1007/s00432-007-0274-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-007-0274-1

Keywords

Search

Navigation