title: Bortezomib has little ex vivo activity in chronic myeloid leukemia: individual tumor response testing comparative study in acute and chronic myeloid leukemia.
abstract: OBJECTIVE
  Resistance to imatinib is one of the most important issues in treatment of chronic myeloid leukemia (CML) patients. The objective of the study was to analyze the ex vivo drug resistance profile to bortezomib and 22 other antileukemic drugs, including three tyrosine kinase inhibitors (TKIs), in CML in comparison to acute myeloid leukemia (AML).
  
  
  METHODS
  A total of 82 patients entered the study, including 36 CML and 46 AML adults. Among CML patients, 19 had advanced disease, 16 were resistant to imatinib, and 6 had ABL-kinase domain mutations. The ex vivo drug resistance profile was studied by the MTT assay.
  
  
  RESULTS
  CML CELLS WERE MORE RESISTANT THAN AML BLASTS TO THE FOLLOWING DRUGS: prednisolone, vincristine, doxorubicin, etoposide, melphalan, cytarabine, fludarabine, thiotepa, 4-HOO-cyclophosphamide, thioguanine, bortezomib, topotecan, and clofarabine. CML cells were 2-fold more sensitive to busulfan than AML cells. CML patients with clinical imatinib resistance had higher ex vivo resistance to vincristine, daunorubicin, etoposide, and busulfan. No significant differences to all tested drugs, including TKIs, were observed between CML patients with non-advanced and advanced disease. CML patients with mutation had higher ex vivo resistance to vincristine, idarubicin, thiotepa, and busulfan.
  
  
  CONCLUSIONS
  CML cells are ex vivo more resistant to most drugs than acute myeloid leukemia blasts. Busulfan is more active in CML than AML cells. In comparison to AML cells, bortezomib has little ex vivo activity in CML cells. No differences between CML subgroups in sensitivity to 3 tested TKIs were detected.
authors.affiliation: Department of Pediatric Hematology and Oncology, Collegium Medicum , Nicolaus Copernicus University, Bydgoszcz, Poland ; Both authors contributed equally to the study.
authors.forename: Jan
authors.initials: J
authors.lastname: Styczyński
authors.forename: Lidia
authors.initials: L
authors.lastname: Gil
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Czyżewski
authors.forename: Beata
authors.initials: B
authors.lastname: Kołodziej
authors.forename: Beata
authors.initials: B
authors.lastname: Kuryło-Rafińska
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Michał
authors.initials: M
authors.lastname: Gniot
authors.forename: Maria
authors.initials: M
authors.lastname: Lewandowska
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
keywords: MTT assay; chronic myeloid leukemia; drug resistance; drug sensitivity