Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements

Tadeusz Styczyński; Beata Kołodziej; Beata Rafińska; Małgorzata Kubicka; Krzysztof Czyżewski; Robert Dębski; Andrzej Kołtan; Sylwia Kołtan; Monika Pogorzała; Anna Krenska; Izabela Pałgan; Katarzyna Dylewska; Agnieszka Gaca; Elżbieta Grześk; Barbara Tejza; Katarzyna Jankowska; Karolina Dulęba; Anna Hagner; Natalia Bartoszewicz; Ewa Demidowicz; Aldona Rudzka-Gockiewicz; Joanna Szczepanek; Andrzej Kurylak; Krystyna Soszyńska; Barbara Mucha; Olga Haus; Mariusz Wysocki

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ISSN: 1428-2526

Contemporary Oncology/Współczesna Onkologia

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7/2007
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abstract:

Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse – relation to cell cycle and gene rearrangements

Tadeusz Styczyński

,

Beata Kołodziej

,

Beata Rafińska

,

Małgorzata Kubicka

,

Krzysztof Czyżewski

,

Robert Dębski

,

Andrzej Kołtan

,

Sylwia Kołtan

,

Monika Pogorzała

,

Anna Krenska

,

Izabela Pałgan

,

Katarzyna Dylewska

,

Agnieszka Gaca

,

Elżbieta Grześk

,

Barbara Tejza

,

Katarzyna Jankowska

,

Karolina Dulęba

,

Anna Hagner

,

Natalia Bartoszewicz

,

Ewa Demidowicz

,

Aldona Rudzka-Gockiewicz

,

Joanna Szczepanek

,

Andrzej Kurylak

,

Krystyna Soszyńska

,

Barbara Mucha

,

Olga Haus

,

Mariusz Wysocki

Współczesna Onkologia (2007) vol. 11; 7 (367–375)

Online publish date: 2007/10/02

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AMA

Styczyński T, Kołodziej B, Rafińska B, et al. Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements. Contemporary Oncology/Współczesna Onkologia. 2007;11(7):367-375.

APA

Styczyński, T., Kołodziej, B., Rafińska, B., Kubicka, M., Czyżewski, K.,  & Dębski, R. et al. (2007). Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements. Contemporary Oncology/Współczesna Onkologia, 11(7), 367-375.

Chicago

Styczyński, Tadeusz, Beata Kołodziej, Beata Rafińska, Małgorzata Kubicka, Krzysztof Czyżewski, Robert Dębski,  and Andrzej Kołtan et al. 2007. "Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements". Contemporary Oncology/Współczesna Onkologia 11 (7): 367-375.

Harvard

Styczyński, T., Kołodziej, B., Rafińska, B., Kubicka, M., Czyżewski, K., Dębski, R., Kołtan, A., Kołtan, S., Pogorzała, M., Krenska, A., Pałgan, I., Dylewska, K., Gaca, A., Grześk, E., Tejza, B., Jankowska, K., Dulęba, K., Hagner, A., Bartoszewicz, N., Demidowicz, E., Rudzka-Gockiewicz, A., Szczepanek, J., Kurylak, A., Soszyńska, K., Mucha, B., Haus, O.,  and Wysocki, M. (2007). Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements. Contemporary Oncology/Współczesna Onkologia, 11(7), pp.367-375.

MLA

Styczyński, Tadeusz et al. "Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements." Contemporary Oncology/Współczesna Onkologia, vol. 11, no. 7, 2007, pp. 367-375.

Vancouver

Styczyński T, Kołodziej B, Rafińska B, Kubicka M, Czyżewski K, Dębski R et al. Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse  – relation to cell cycle and gene rearrangements. Contemporary Oncology/Współczesna Onkologia. 2007;11(7):367-375.

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.

keywords:

Combined in vitro drug resistance profile in childhood acute lymphoblastic leukemia on diagnosis and at relapse – relation to cell cycle and gene rearrangements

drug resistance, acute lymphoblastic leukaemia, gene rearrangements, cytogenetics