@Article{Styczyński2007,
journal="Contemporary Oncology/Współczesna Onkologia",
issn="1428-2526",
volume="11",
number="7",
year="2007",
title="Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  \– relation to cell cycle and gene rearrangements",
abstract="Background: The clinical effect of chemotherapy is dependent on drug pharmacokinetics, cellular response and regenerative potential of residual cells.  Objective: Analysis of in vitro drug resistance in childhood acute lymphoblastic leukaemia (ALL) on diagnosis and at relapse, with respect to cell cycle study and gene rearrangements.  Material and methods: A total of 116 patients entered the study, including 106 de novo and 23 relapsed children; in 13 patients paired analysis was performed. In vitro drug resistance profile for 21 compounds was done by the MTT assay, including combined drug resistance profile for prednisolone, vincristine and L-asparaginase (PVA score). DNA index and cell cycle phases were analyzed by flow cytometry. Gene rearrangement study was done by FISH and PCR.  Results: PVA score showed higher in vitro drug resistance of lymphoblasts at relapse and in T-ALL. Relapsed lymphoblasts were more in vitro resistant to prednisolone, dexamethasone and thioguanine. Paired analysis showed good sensitivity at relapse for cytarabine and cladribine. T-ALL lymphoblasts were more in vitro resistant than common-ALL to vincristine, cytarabine, fludarabine and cladribine. Relapsed common-ALL were more in vitro resistant than common-ALL at first diagnosis to fludarabine and thioguanine. Lymphoblasts with TEL-AML1 rearrangement were more drug sensitive to L-asparaginase; lymphoblasts with MLL rearrangements were more sensitive to cytarabine and idarubicin.  No differences in drug resistance were found for BCR-ABL lymphoblasts. No unambiguous relations were found between cell cycle parameters and cellular drug resistance.  Conclusion: In vitro drug resistance in childhood ALL is related to biological features of lymphoblasts.",
author="Styczyński, Tadeusz
and Kołodziej, Beata
and Rafińska, Beata
and Kubicka, Małgorzata
and Czyżewski, Krzysztof
and Dębski, Robert
and Kołtan, Andrzej
and Kołtan, Sylwia
and Pogorzała, Monika
and Krenska, Anna
and Pałgan, Izabela
and Dylewska, Katarzyna
and Gaca, Agnieszka
and Grześk, Elżbieta
and Tejza, Barbara
and Jankowska, Katarzyna
and Dulęba, Karolina
and Hagner, Anna
and Bartoszewicz, Natalia
and Demidowicz, Ewa
and Rudzka-Gockiewicz, Aldona
and Szczepanek, Joanna
and Kurylak, Andrzej
and Soszyńska, Krystyna
and Mucha, Barbara
and Haus, Olga
and Wysocki, Mariusz",
pages="367--375",
url="https://www.termedia.pl/Combined-in-vitro-drug-resistance-profile-in-childhood-acute-lymphoblastic-leukemia-on-diagnosis-and-at-relapse-8211-relation-to-cell-cycle-and-gene-rearrangements,3,9044,1,1.html"
}