ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis

• Published in: Leukemia research Vol. 27; no. 12; pp. 1163 - 1166
• Main Authors: Sacha, Tomasz, Hochhaus, Andreas, Hanfstein, Benjamin, Müller, Martin C., Rudzki, Zbigniew, Czopek, Jacek, Wolska-Smoleń, Teresa, Czekalska, Sylwia, Salamanchuk, Zoriana, Jakóbczyk, Małgorzata, Skotnicki, Aleksander B.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2003; Elsevier Science
• Subjects: ABL mutation; Adenosine Triphosphate - metabolism; Adult; Amino Acid Sequence; Antineoplastic agents; Base Sequence; BCR–ABL; Benzamides; Biological and medical sciences; Blast crisis; Blast Crisis - pathology; Chemotherapy; Chronic myelogenous leukaemia; Drug Resistance, Neoplasm - genetics; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Humans; Imatinib; Imatinib Mesylate; Karyotyping; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology; Male; Medical sciences; Molecular Sequence Data; Pharmacology. Drug treatments; Piperazines - therapeutic use; Point Mutation - genetics; Proto-Oncogene Proteins c-abl - genetics; Proto-Oncogene Proteins c-abl - metabolism; Pyrimidines - therapeutic use; Resistance; Sequence Homology, Nucleic Acid; aa; BC; BCR–ABL; G6PD; Imatinib; CML; s.c; BM; α-IFN; p.o; Resistance; Chronic myelogenous leukaemia; Ld Ara-C; PB; IBP; RT-PCR; Ph; Blast crisis; ABL mutation; HLA; Chromosomal aberration; Antineoplastic agent; Male; Blast transformation; Myeloproliferative syndrome; Chronic myelocytic leukemia; Genetics; Adult; Protein-tyrosine kinase; Hybrid gene; Protooncogene; Chromosome translocation; Human; Treatment resistance; Enzyme; Transferases; BCR-ABL; Enzyme inhibitor; Malignant hemopathy; Philadelphia chromosome; Case study; Chemotherapy; Chronic; Treatment; C-Onc gene; Point mutation; Cytogenetics; Abnormal chromosome
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/S0145-2126(03)00117-6

Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR–ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.