title: Determination of the optimal chemotherapy drugs pretreatment time through cultivation of hemopoietic cells in CML-patients treated with tyrosine kinase inhibitors.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Centre of Molecular and Cell Research of the National University "Kyiv-Mohyla Academy", Kyiv 04655, Ukraine.
authors: I O
authors: IO
authors: Zhaleiko
authors: SI "Institute of Hematology and Transfusiology" of the NAMS of Ukraine, Kyiv 04060, Ukraine.
authors: T P
authors: TP
authors: Perekhrestenko
authors: Centre of Molecular and Cell Research of the National University "Kyiv-Mohyla Academy", Kyiv 04655, Ukraine.
authors: D I
authors: DI
authors: Bilko
authors: National Research Center for Radiation Medicine, NAMS of Ukraine, Kyiv, Ukraine.
authors: I S
authors: IS
authors: Dyagil
authors: Centre of Molecular and Cell Research of the National University "Kyiv-Mohyla Academy", Kyiv 04655, Ukraine.
authors: N M
authors: NM
authors: Bilko
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects*; D002066:Busulfan / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy*; D061251:Primary Cell Culture; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D002066:Busulfan; D006918:Hydroxyurea