title: Ex vivo drug resistance profile in childhood acute myelogenous leukemia: no drug is more effective in comparison to acute lymphoblastic leukemia.
abstract: Therapy results in childhood acute myelogenous leukemia (AML) differ from those of acute lymphoblastic leukemia (ALL). Cellular drug resistance might be one of the reasons of therapy failure in AML. The aim of the study was the analysis of ex vivo drug resistance profile in childhood initial and relapsed AML in comparison to initial ALL. Fifty-three AML samples were tested for chemosensitivity and results were compared with those of 106 initial ALL samples. Ex vivo drug resistance was tested by means of the MTT assay. Up to 29 cytotoxic drugs were tested for each patient. When compared to de nova ALL samples, myeloblasts from initial AML samples were significantly more resistant to most tested drugs, except cytarabine, mercaptopurine and thioguanine. Relapsed AML samples, in relation to initial AML samples, showed comparable sensitivity to cytarabine, idarubicin, fludarabine and cladribine. Patients, who have died due to refractory or relapsing disease, were already on first diagnosis 2-fold more resistant to cytarabine, 6.4-fold more resistant to cisplatin and 3-fold more resistant to carboplatin, when compared to those who stay in remission. Resistance to prednisolone was observed in 85% initial and all relapsed AML samples, in comparison to 33% of ALL samples. Resistance to cytarabine occurred in 2.1% of ALL and 12% of AML cases while a patient with Down syndrome presented the most sensitive drug resistance profile. In conclusion this study shows that no drug was found which, on average, was more effective in AML than in ALL samples. The sensitivity of myeloblasts to platinum derivatives might have prognostic value.
authors.affiliation: Department of Pediatric Hematology and Oncology, Medical University Bydgoszcz, Bydgoszcz, Poland. jan_styczynski@kki.net.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Styczynski
authors.forename: Mariusz
authors.initials: M
authors.lastname: Wysocki
authors.forename: Robert
authors.initials: R
authors.lastname: Debski
authors.forename: Edyta
authors.initials: E
authors.lastname: Juraszewska
authors.forename: Iwona
authors.initials: I
authors.lastname: Malinowska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Stanczak
authors.forename: Anna
authors.initials: A
authors.lastname: Ploszynska
authors.forename: Jolanta
authors.initials: J
authors.lastname: Stefaniak
authors.forename: Benigna
authors.initials: B
authors.lastname: Mazur
authors.forename: Tomasz
authors.initials: T
authors.lastname: Szczepanski
mesh_terms: D016190:Carboplatin / Q000627:therapeutic use; D002470:Cell Survival; D002648:Child; D002945:Cisplatin / Q000627:therapeutic use; D004396:Coloring Agents / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016190:Carboplatin; C022616:thiazolyl blue; D002945:Cisplatin