Drug Resistance in Leukemia and Lymphoma III: Proceedings of the Third International Symposium Held in Amsterdam, the Netherlands, March 4-7, 1998 (Advances ... Experimental Medicine and Biology Book 457)

Cellular drug resistance is a major limitation to the success of chemotherapy of leu­ kemia and lymphoma. The importance of this has now been recognized by both clinicians and scientists. It is of utmost importance to bridge the gap between laboratory and clinic in this field of research. This is the main purpose of the series of International Symposia on Drug Resistance in Leukemia and Lymphoma. These are held every three years in Am­ sterdam, The Netherlands, since 1992. This book contains the proceedings of the third of these meetings, organised in 1998. The book covers all important aspects of drug resistance in leukemia and lymphoma, both in the form of extensive reviews as in manuscripts describing original data. General mechanisms of resistance are discussed, including the drug resistance related proteins p­ glycoprotein, MRP (multi-drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases. Moreover, more drug type-specific mechanisms of resistance are a topic, such as for glucocorticoids and antifolates. Much in­ formation is provided on apoptosis and its regulators, and on the results of cell culture drug resistance assays. Several papers focus on the modulation or circumvention of drug resistance. Front Matter....Pages i-xiv MDR1/P-GP Expression as A Prognostic Factor in Acute Leukemias....Pages 1-9 Clinical Significance of P-Glycoprotein (P-gp) Expression in Childhood Acute Lymphoblastic Leukemia....Pages 11-19 Prognostic Value of P-gp Expression and Related Function in Childhood Acute Leukemia....Pages 21-28 Comparison of P-Glycoprotein Expression and Function with in vitro Sensitivity to Anthracyclines in AML....Pages 29-33 Quinine Improves Results of Intensive Chemotherapy (IC) in Myelodysplastic Syndromes (MDS) Expressing P-Glycoprotein (PGP)....Pages 35-46 Treatment of Poor Prognosis AML Patients Using PSC833 (Valspodar) Plus Mitoxantrone, Etoposide, and Cytarabine (PSC-MEC)....Pages 47-56 Assessment of P-Glycoprotein Expression by Immunocytochemistry and Flow Cytometry Using Two Different Monoclonal Antibodies Coupled with Functional Efflux Analysis in 34 Patients with Acute Myeloid Leukemia....Pages 57-63 Preliminary Immunocytochemical Studies of MDR-1 and MDR-3 Pgp Expression in B-Cell Leukaemias....Pages 65-70 A Mutation in the Promoter of the Multidrug Resistance Gene ( MDR1 ) in Human Hematological Malignancies may Contribute to the Pathogenesis of Resistant Disease....Pages 71-75 Reproducible Flow Cytometric Methodology for Measuring Multidrug Resistance in Leukaemic Blasts....Pages 77-88 Natural Fluorescence Imaging of Leukemic Cells for Studying Uptake and Retention of Anthracyclines....Pages 89-94 Artificial Neural Networks as Versatile Tools for Prediction of MDR-Modulatory Activity....Pages 95-105 Discordance of P-Glycoprotein Expression and Function in Acute Leukemia....Pages 107-118 Multidrug Resistance Related Proteins in Primary Cutaneous Lymphomas....Pages 119-131 The Lung Resistance Protein (LRP) Predicts Poor Outcome in Acute Myeloid Leukemia....Pages 133-139 MRP Expression in Acute Myeloid Leukemia....Pages 141-150 Evidence for Functional Discrimination Between Leukemic Cells Overexpressing Multidrug-Resistance Associated Protein and P-Glycoprotein....Pages 151-160 Both Pgp and MRP1 Activities Using Calcein-AM Contribute to Drug Resistance in AML....Pages 161-175 Absolute Levels of MDR-1, MRP, and BCL-2 MRNA and Tumor Remission in Acute Leukemia....Pages 177-185 Multidrug Resistance Protein MRP1, Glutathione, and Related Enzymes....Pages 187-198 Glutathione and the Regulation of Cell Death....Pages 199-203 Evidence for the Involvement of the Glutathione Pathway in Drug Resistance in AML....Pages 205-209 Glutathione in Childhood Acute Leukaemias....Pages 211-216 Apoptosis....Pages 217-236 Activation of Apoptosis Pathways by Anticancer Drugs....Pages 237-244 BCL-2 Stimulates Apoptin®-Induced Apoptosis....Pages 245-249 CD95 (FAS/APO-1) Antigen is a New Prognostic Marker of Blast Cells of Acute Lymphoblastic Leukaemia Patients....Pages 251-258 Inhibition of FAS/FAS-Ligand Does Not Block Chemotherapy-Induced Apoptosis in Drug Sensitive and Resistant Cells....Pages 259-266 Effects of Parp Inhibition on Drug and FAS-Induced Apoptosis in Leukaemic Cells....Pages 267-279 Apoptotic Fraction in Childhood All Assessed by DNA in situ Labelling is Ploidy Independent....Pages 281-287 PCNA Bearing Structures are Retained in Apoptotic Phase of Childhood All Cell Cycle....Pages 289-296 Apoptosis Corrected Proliferation Fraction in Childhood All is Related to Karyotype....Pages 297-303 Proliferation and Apoptosis Does Not Affect Presenting White Cell Count in Childhood All....Pages 305-312 Apoptosis by Anthracyclines at Therapeutic Concentrations in MDR1+ Human Leukemic Cells....Pages 313-324 BCL-2 Expression in Childhood Leukemia Versus Spontaneous Apoptosis, Drug Induced Apoptosis, and in vitro Drug Resistance....Pages 325-333 Comparison of BCL-2 and Bax Protein Expression with in vitro Sensitivity to ARA-C and 6TG in AML....Pages 335-340 Synthetic Cyclin Dependent Kinase Inhibitors....Pages 341-353 Factors Contributing to the Resistance to Apoptosis Induced by Topoisomerase I Inhibitors in Vincristine Resistant Cells....Pages 355-363 Two Distinct Modes of Oncoprotein Expression During Apoptosis Resistance in Vincristine and Daunorubicin Multidrug-Resistant HL60 Cells....Pages 365-381 Genetic Abnormalities and Drug Resistance in Acute Lymphoblastic Leukemia....Pages 383-389 Resistance Testing and Mechanisms of Resistance in Childhood Leukemia....Pages 391-395 Pharmacokinetics of Anticancer Drugs In Vitro....Pages 397-407 Down Syndrome and Acute Myeloid Leukemia....Pages 409-414 Cellular Drug Resistance in Childhood Acute Myeloid Leukemia....Pages 415-421 Is In Vitro Sensitivity of Blast Cells Correlated to Therapeutic Effect in Childhood Acute Lymphoblastic Leukemia?....Pages 423-428 In Vitro Cytotoxic Drug Activity and In Vivo Pharmacokinetics in Childhood Acute Myeloid Leukemia....Pages 429-435 Prognosis in Adult AML is Precisely Predicted by the Disc-Assay Using the Chemosensitivity-Index C I ....Pages 437-444 Drug Resistance Testing of Acute Myeloid Leukemia in Adults Using the MTT Assay....Pages 445-452 MTT Assay for Drug Resistance in Childhood Acute Leukemia and Effect of Cyclosporin and Interferon....Pages 453-459 Differential Antileukemic Activity of Prednisolone and Dexamethasone in Freshly Isolated Leukemic Cells....Pages 461-471 Activity of Vinorelbine on B-Chronic Lymphocytic Leukemia Cells In Vitro ....Pages 473-476 Studies of Some Mechanisms of Drug Resistance in Chronic Myeloid Leukemia (CML)....Pages 477-488 Clinical Sensitivity to Anthracyclines in PH/BCR+ Acute Lymphoblastic Leukemia....Pages 489-499 Differential Kinetics of Drug Resistance in Human Leukaemic Cells Measured by SCGE/CLSM....Pages 501-508 Demonstration of Differences in Drug Resistance by Direct Testing of DNA Excision Repair Activity Following Standard and Liposomal Daunorubicin Exposure in Normal Paediatric Marrow Using High Resolution CLSM....Pages 509-516 Microsatellite Instability Assessment in Prediction of Drug Resistance in Childhood Burkitt’s and Large Cell Diffuse Malignant Non-Hodgkin Lymphoma (MNHL)....Pages 517-525 High Resolution Confocal Laser Scanning Microscopy Analysis of DNA Excision Repair Capability in Small Volume Marrow Samples Exposed to DNA Directed Treatment Moieties....Pages 527-535 Defining the Optimal Dosage of Methotrexate for Childhood Acute Lymphoblastic Leukemia....Pages 537-541 Mechanisms of Methotrexate Resistance in Acute Leukemia....Pages 543-550 Lack of Cross-Resistance Between Prednisolone and Methotrexate in Childhood Acute Lymphoblastic Leukemia?....Pages 551-555 New Developments in the Treatment of Acute Myeloid Leukemia....Pages 557-565 Aphidicolin Markedly Increases the In Vitro Sensitivity to ARA-C of Blast Cells From Patients with AML....Pages 567-570 Common Resistance Mechanisms to Nucleoside Analogues in Variants of the Human Erythroleukemic Line K562....Pages 571-577 Expression of DNA Mismatch Repair Proteins in Acute Lymphoblastic Leukaemia and Normal Bone Marrow....Pages 579-583 Effects of CSFS and their Combinations with Chemotherapeutic Agents (CH) on Leukemic Blasts (LB) in Children (MTT-Assay)....Pages 585-592 Glucocorticosteroid Therapy in Childhood Acute Lymphoblastic Leukemia....Pages 593-605 Glucocorticoid Induced Apoptosis in Leukemia....Pages 607-614 Glucocorticoid Resistance and the AP-1 Transcription Factor in Leukaemia....Pages 615-619 The Three Asparaginases....Pages 621-629 Back Matter....Pages 631-638 This volume covers all important aspects of drug resistance in leukemia and lymphoma. General mechanisms of resistance are discussed, including the drug resistance related proteins, MRP (multi drug resistance protein) and LRP (lung resistance protein), and the role of glutathione and glutathione-S-transferases, as well as drug-specific mechanisms of resistance, apoptosis and its regulators and modulation of drug resistance