Resistance Testing and Mechanisms of Resistance in Childhood Leukemia

Studies from Amsterdam
  • R. Pieters
  • G. J. L. Kaspers
  • N. L. Ramakers-van Woerden
  • M. L. den Boer
  • M. G. Rots
  • Ch. M. Zwaan
  • E. G. Haarman
  • A. J. P. Veerman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 457)

Abstract

The prognosis of children with leukemia has improved dramatically due to the development of effective combination chemotherapy. Nevertheless, about 25% of children with acute lymphobalstic leukemia (ALL) and 50% of children with acute myeloid leukemia (AML) die of resistant or relapsed disease. On the other hand, patients who are curable with relatively mild chemotherapy as used in the seventies, will nowadays be overtreated and suffer from unnecessary side-effects. This is due to the fact that therapy has been intensified for all patients in (successful) attempts to cure an increasing number of children.Therefore, it is of the highest importance to identify children with highly sensitive leukemia that can be cured with minimal therapy and children who need specifically intensified therapy. Our research program focusses on the relation between molecular biological characteristics, drug resistance and prognosis in pediatric oncology. Here, results from some recent and currently ongoing studies in leukemia will be described.

Keywords

Leukemia Methotrexate Glucocorticoid Prednisolone Vincristine 

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References

  1. 1.
    Pieters R, Loonen AH, Huismans DR, Broekema GJ, Dirven MWJ, Heyenbrok MW, Hählen K, Veerman AJP. In vitro drug sensitivity of cells from children with leukemia using the MTT assay with improved culture conditions. Blood 1990; 76:2327–2336.PubMedGoogle Scholar
  2. 2.
    Pieters R, Huismans DR, Loonen AH, Hählen K, Van der Does-van den Berg A, Van Wering ER, Veerman AJP. Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia. Lancet 1991; 338:399–403.PubMedCrossRefGoogle Scholar
  3. 3.
    Kaspers GJL, Veerman AJP, Pieters R, Van Zantwijk CH, Smets LA, Van Wering ER, Van der Does-van den Berg A. In vitro cellular drug resistance and prognosis in newly diagnosed childhood acute lymphoblastic leukemia. Blood 1997; 90:2723–2729PubMedGoogle Scholar
  4. 4.
    Klumper E, Ossenkoppele GJ, Pieters R, Huismans DR, Loonen AH, Rottier MMA, Westra G, Veerman AJP. In vitro resistance to cytosine arabinoside, not to daunorubicin, is associated with the risk of relapse in de novo acute myeloid leukaemia. Br J Haematol 1996; 93:903–910.PubMedCrossRefGoogle Scholar
  5. 5.
    Klumper E, Pieters R, Veerman AJP, Huismans DR, Loonen AH, Hählen K, Kaspers GJL, Van Wering ER, Hartmann R, Henze G. In vitro cellular drug resistance in children with relapsed/refractory acute lymphoblastic leukemia. Blood 1995; 86:3861–3868PubMedGoogle Scholar
  6. 6.
    Kaspers GJL, Smets LA, Pieters R, Van Zantwijk CH, De Waal FC, Van Wering ER, Veerman AJP. Favorable prognosis of hyperdiploid common acute lymphoblastic leukemia may be explained by sensitivity to antimetabolites and other drugs: results of an in vitro study. Blood 1995; 85:751–756.PubMedGoogle Scholar
  7. 7.
    Pieters R, Kaspers GJL, Van Wering ER, Huismans DR, Loonen AH, Hählen K, Veerman AJP. Cellular drug resistance profiles that might explain the prognostic value of immunophenotype and age in childhood acute lymphoblastic leukemia. Leukemia 1993; 7:392–397.PubMedGoogle Scholar
  8. 8.
    Kaspers GJL, Pieters R, Van Zantwijk CH, Van Wering ER, Veerman AJP. Clinical and cell biological features related to cellular drug resistance of childhood acute lymphoblastic leukemia cells. Leuk Lymphoma 1995; 19:407–416.PubMedCrossRefGoogle Scholar
  9. 9.
    Pieters R, Den Boer ML, Durian M, Janka-Schaub GE, Schmiegelow K, Kaspers GJL, Van Wering ER, Veerman AJR Relation between age, immunophenotype and in vitro drug resistance in 395 children with acute lymphoblastic leukemia — implications for treatment of infants. Leukemia 1998; 12:1344–1348.PubMedCrossRefGoogle Scholar
  10. 10.
    Pieters R, Huismans DR, Loonen AH, Peters GJ, Hählen K, Van der Does-van den Berg A, Van Wering ER, Veerman AJP. Hypoxanthine-guanine phosphoribosyl-transferase in childhood leukemia: relation with immunophenotype, in vitro drug resistance and clinical prognosis. Int J Cancer 1992; 51:213–217.PubMedCrossRefGoogle Scholar
  11. 11.
    Pieters R, Thompson LF, Broekema GJ, Huismans DR, Peters GJ, Pals ST, Horst E, Hählen K, Veerman AJR Expression of 5′-nucleotidase (CD73) related to other differentiation antigens in leukemias of B-cell lineage. Blood 1991; 78:488–492.PubMedGoogle Scholar
  12. 12.
    Pieters R, Huismans DR, Loonen AH, Peters GJ, Hählen K, Van der Does-van den Berg A, Van Wering ER, Veerman AJP. Relation of 5′-nucleotidase and phosphatase activities with immunophenotype, drug resistance and clinical prognosis in childhood leukemia. Leuk Res 1992; 16:873–880.PubMedCrossRefGoogle Scholar
  13. 13.
    Den Boer ML, Pieters R, Kazemier KM, Rottier MMA, Zwaan ChM, Kaspers GJL, Janka-Schaub GE, Henze G, Creutzig U, Scheper RJ, Veerman AJP. Relationship between major vault protein/lung resistance protein, multidrug resistance-associated protein, P-glycoprotein expression, and drug resistance in childhood leukemia. Blood 1998; 91:2092–2098.Google Scholar
  14. 14.
    Klumper E, Giaccone G, Pieters R, Broekema G, Van Ark-Otte J, Van Wering ER, Kaspers GJL, Veerman AJP. Topoisomerase IIα gene expression in childhood acute lymphoblastic leukemia. Leukemia 1995; 9:1653–1660.PubMedGoogle Scholar
  15. 15.
    Kaspers GJL, Pieters R, Van Zantwijk CH, Van Wering ER, Van der Does-van den Berg A, Veerman AJP. Prednisolone resistance in childhood acute lymphoblastic leukemia: vitro-vivo correlations and cross-resistance to other drugs. Blood 1998; 92:1–8.Google Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • R. Pieters
    • 1
  • G. J. L. Kaspers
    • 1
  • N. L. Ramakers-van Woerden
    • 1
  • M. L. den Boer
    • 1
  • M. G. Rots
    • 1
  • Ch. M. Zwaan
    • 1
  • E. G. Haarman
    • 1
  • A. J. P. Veerman
    • 1
  1. 1.Department of Pediatric Hematology/OncologyUniversity Hospital Vrije UniversiteitAmsterdamThe Netherlands

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