Document Detail


Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.
MedLine Citation:
PMID:  20010464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: 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. OBJECTIVES: 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). PATIENTS AND 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:
Krzysztof Lewandowski; Krzysztof Warzocha; Andrzej Hellmann; Aleksander Skotnicki; Witold Prejzner; Kajetana Foryciarz; Tomasz Sacha; Micha? Gniot; Miros?aw Majewski; Iwona Solarska; Grazyna Nowak; Bartosz Wasag; Miko?aj Kobelski; Cezary Scibiorski; Marek Siemiatkowski; Maria Lewandowska; Mieczys?aw Komarnicki
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Polskie Archiwum Medycyny Wewn?trznej     Volume:  119     ISSN:  1897-9483     ISO Abbreviation:  Pol. Arch. Med. Wewn.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-12-17     Completed Date:  2010-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0401225     Medline TA:  Pol Arch Med Wewn     Country:  Poland    
Other Details:
Languages:  eng     Pagination:  789-94     Citation Subset:  IM    
Affiliation:
Department of Hematology, Poznan University of Medical Sciences, Pozna?, Poland. krzysztof.lewandowski@sk1.am.poznan.pl
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antineoplastic Agents / therapeutic use*
Chromatography, High Pressure Liquid
DNA Mutational Analysis
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / genetics*
Female
Fusion Proteins, bcr-abl / genetics*
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics*
Male
Middle Aged
Neoplasm Staging
Piperazines / therapeutic use*
Poland
Protein Kinase Inhibitors / therapeutic use*
Pyrimidines / therapeutic use*
Treatment Outcome
Young Adult
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 152459-95-5/imatinib

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