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Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias-correlation to the expression of multidrug resistance proteins

Item Type:Article
Title:Chemo- and radiation sensitivity of xenografted acute lymphoblastic leukemias-correlation to the expression of multidrug resistance proteins
Creators Name:Fichtner, I. and Paal, K. and Borgmann, A. and Badiali, L. and Wurm, R. and Henze, G.
Abstract:The aim of our study was to characterise, for the first time, the chemo- and radiation sensitivity of seven pediatric acute lymphoblastic leukemias xenotransplanted into immunodeficient NOD/SCID mice and to correlate the findings with the expression of three drug resistance proteins, P-glycoprotein (P-gp), multidrug resistance- associated protein (MRP1) and lung resistance protein (LRP). Mice were treated with single drugs used in clinical protocols: daunorubicin, doxorubicin, cyclophosphamide, vincristine, cytarabine, asparaginase and methotrexate. Two ALL samples, established from primarily diagnosed patients, responded to 5 or 6 of the tested cytostatics, respectively, while 3 out of 5 ALLs from relapse patients were only sensitive towards 2-4 drugs tested. Daunorubicin was more efficient than doxorubicin. The response of xenografted ALL toward vincristine and cyclophosphamide was inversely correlated with the expression of P-gp, LRP and MRP1 (R 2 = 0.71, 0.70 and 0.64 for vincristine and 0.44, 0.70 and 0.60 for cyclophosphamide). A good correlation could be detected between the expression of P-gp and LRP (R 2 = 0.88), P-gp and MRP1 (R 2 = 0.75) and LRP and MRP1 (R 2 = 0.90). The highest co-expression of the drug resistance proteins in the leukemia ALL-SCID 6 coincided with a high resistance to radiation and chemotherapy. Prediction of the individual drug resistance profile of a patient on the basis of results from the ALL-SCID xenograft studies was not possible because of the relatively long time necessary and because of the changes in the expression of P-gp, LRP and MRP1 during the murine generations. We conclude that in the drug resistance phenotype of ALL not only the above mentioned proteins but a variety of different molecules are involved.
Keywords:Acute Lymphoblastic Leukemia, NOD/SCID Mice, Chemosensitivity, Radiation, Multidrug Resistance, Animals, Mice
Source:Anticancer Research
ISSN:0250-7005
Publisher:Delinassios (Greece)
Volume:23
Number:3
Page Range:2657-2664
Date:May 2003
PubMed:View item in PubMed

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