Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors

Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors

Background: Targeted therapy drugs, including imatinib, are used for inhibiting the marker oncoprotein of chronic myeloid leukemia — BCR-ABL tyrosine kinase. However, in some patients the drug resistance can emerge too rapidly and a previous treatment with chemotherapy drugs can lead to formation of...

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Дата:2014
Автори: Zhaleiko, I.O., Perekhrestenko, T.P., Bilko, D.I., Dyagil, I.S., Bilko, N.M.
Формат: Стаття
Мова:English
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2014
Назва видання:Experimental Oncology
Теми:
Original contributions
Онлайн доступ:http://dspace.nbuv.gov.ua/handle/123456789/145345
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors / I.O. Zhaleiko, T.P. Perekhrestenko, D.I. Bilko, I.S. Dyagil, N.M. Bilko // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 112-116. — Бібліогр.: 19 назв. — англ.

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spelling irk-123456789-1453452019-01-21T01:24:22Z Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors Zhaleiko, I.O. Perekhrestenko, T.P. Bilko, D.I. Dyagil, I.S. Bilko, N.M. Original contributions Background: Targeted therapy drugs, including imatinib, are used for inhibiting the marker oncoprotein of chronic myeloid leukemia — BCR-ABL tyrosine kinase. However, in some patients the drug resistance can emerge too rapidly and a previous treatment with chemotherapy drugs can lead to formation of resistance. Aim: To evaluate the influence of drugs that were used prior to the imatinib on the performance of the functional activity of bone marrow cells from chronic myeloid leukemia patients and their indivi­dual responses to therapy. Methods: Bone marrow aspirate from 57 patients, who were getting busulfan (19 patients) or hydroxycarbamide (38 patients) prior to imatinib was studied with cytogenetic and tissue culture methods in vitro. Results: Obtained data suggested that pretreatment with busulfan, regardless of duration, negatively affects the response to further therapy with imatinib. Instead, after using hydroxycarbamide as a previous therapy for six month, there was optimal response to imatinib. In those cases when duration of pretreatment with hydroxycarbamide was increased to a year or more, there was a suboptimal response and a resistance to imatinib therapy. In addition, there was a positive correlation between the number of cell aggregates (colonies and clusters) in semisolid agar and the duration of a prior treatment with hydroxycarbamide, if previous therapy did not exceed 20 months. With an increase of pretreatment terms to 21 months or more, such a correlation was not observed. Conclusions: These results suggest that chemotherapeutic agents (busulfan and hydroxycarbamide) may additionally contribute to the accumulation of mutations in the genome of leukemic cell clone affecting the behavior of these cells in vitro. Key Words: chronic myeloid leukemia, imatinib, pretreatment, hydroxycarbamide, busulfan, cell culture in vitro. 2014 Article Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors / I.O. Zhaleiko, T.P. Perekhrestenko, D.I. Bilko, I.S. Dyagil, N.M. Bilko // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 112-116. — Бібліогр.: 19 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145345 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Zhaleiko, I.O.
Perekhrestenko, T.P.
Bilko, D.I.
Dyagil, I.S.
Bilko, N.M.
Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
Experimental Oncology
description Background: Targeted therapy drugs, including imatinib, are used for inhibiting the marker oncoprotein of chronic myeloid leukemia — BCR-ABL tyrosine kinase. However, in some patients the drug resistance can emerge too rapidly and a previous treatment with chemotherapy drugs can lead to formation of resistance. Aim: To evaluate the influence of drugs that were used prior to the imatinib on the performance of the functional activity of bone marrow cells from chronic myeloid leukemia patients and their indivi­dual responses to therapy. Methods: Bone marrow aspirate from 57 patients, who were getting busulfan (19 patients) or hydroxycarbamide (38 patients) prior to imatinib was studied with cytogenetic and tissue culture methods in vitro. Results: Obtained data suggested that pretreatment with busulfan, regardless of duration, negatively affects the response to further therapy with imatinib. Instead, after using hydroxycarbamide as a previous therapy for six month, there was optimal response to imatinib. In those cases when duration of pretreatment with hydroxycarbamide was increased to a year or more, there was a suboptimal response and a resistance to imatinib therapy. In addition, there was a positive correlation between the number of cell aggregates (colonies and clusters) in semisolid agar and the duration of a prior treatment with hydroxycarbamide, if previous therapy did not exceed 20 months. With an increase of pretreatment terms to 21 months or more, such a correlation was not observed. Conclusions: These results suggest that chemotherapeutic agents (busulfan and hydroxycarbamide) may additionally contribute to the accumulation of mutations in the genome of leukemic cell clone affecting the behavior of these cells in vitro. Key Words: chronic myeloid leukemia, imatinib, pretreatment, hydroxycarbamide, busulfan, cell culture in vitro.
format Article
author Zhaleiko, I.O.
Perekhrestenko, T.P.
Bilko, D.I.
Dyagil, I.S.
Bilko, N.M.
author_facet Zhaleiko, I.O.
Perekhrestenko, T.P.
Bilko, D.I.
Dyagil, I.S.
Bilko, N.M.
author_sort Zhaleiko, I.O.
title Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
title_short Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
title_full Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
title_fullStr Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
title_full_unstemmed Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors
title_sort determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in cml-patients treated with tyrosine kinase inhibitors
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2014
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/145345
citation_txt Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors / I.O. Zhaleiko, T.P. Perekhrestenko, D.I. Bilko, I.S. Dyagil, N.M. Bilko // Experimental Oncology. — 2014. — Т. 36, № 2. — С. 112-116. — Бібліогр.: 19 назв. — англ.
series Experimental Oncology
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first_indexed 2025-07-10T21:28:22Z
last_indexed 2025-07-10T21:28:22Z
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