title: Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.
abstract: BACKGROUND
  The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment.
  
  
  OBJECTIVE
  The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM).
  
  
  METHODS
  Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM.
  
  
  RESULTS
  Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM.
  
  
  CONCLUSIONS
  The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.
authors.affiliation: Department of Hematology, Poznan University of Medical Sciences, Poznań, Poland. krzysztof.lewandowski@sk1.am.poznan.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Lewandowski
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Warzocha
authors.forename: Andrzej
authors.initials: A
authors.lastname: Hellmann
authors.forename: Aleksander
authors.initials: A
authors.lastname: Skotnicki
authors.forename: Witold
authors.initials: W
authors.lastname: Prejzner
authors.forename: Kajetana
authors.initials: K
authors.lastname: Foryciarz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Sacha
authors.forename: Michał
authors.initials: M
authors.lastname: Gniot
authors.forename: Mirosław
authors.initials: M
authors.lastname: Majewski
authors.forename: Iwona
authors.initials: I
authors.lastname: Solarska
authors.forename: Grazyna
authors.initials: G
authors.lastname: Nowak
authors.forename: Bartosz
authors.initials: B
authors.lastname: Wasag
authors.forename: Mikołaj
authors.initials: M
authors.lastname: Kobelski
authors.forename: Cezary
authors.initials: C
authors.lastname: Scibiorski
authors.forename: Marek
authors.initials: M
authors.lastname: Siemiatkowski
authors.forename: Maria
authors.initials: M
authors.lastname: Lewandowska
authors.forename: Mieczysław
authors.initials: M
authors.lastname: Komarnicki
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010879:Piperazines / Q000627:therapeutic use*; D011044:Poland; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl