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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-3
pubmed:abstractText
To explore the characteristics of BCR-ABL kinase domain point mutations in Chinese chronic myeloid leukemia (CML) patients, a cohort of 127 patients with hematologic or cytogenetic resistance to imatinib are screened by direct sequencing. Mutations are found in 74 patients (58%). More patients with hematologic resistance show mutations compared to patients with cytogenetic resistance (70% vs 44%, p = 0.002), and more patients with acquired resistance present mutations compared to patients with primary resistance (68% vs 48%, p = 0.031). Frequencies of mutations were similar in early chronic phase (ECP), late chronic phase (LCP), accelerated phase, and blast phase (BP) patients (56%, 58%, 50%, and 69%, respectively; p > 0.05). Overall, 25 mutants are found in 21 amino acid sites, and four of them (I418V, E450A, E453L, and E455K) are first reported here. All patients with these four mutants either progress to or reenter the BP. The most frequent mutant is M244V, followed by Y253H, F359C/V/I, G250E, E255K, and T315I. Only seven patients (9%) have T315I mutants, and all showed hematologic resistance. Three of them were in the ECP and three in the LCP. Look-back studies show that mutants were detected 0-20 (median 7) months ahead of the appearance of clinical resistance in 15 tested patients with acquired resistance. ABL mutations are common in Chinese imatinib-resistant CML patients and are associated with clinical resistance. Chinese patients also seem to have unique profiles in the types and frequencies of some mutants, the disease phases of patients with T315I mutation, and the frequency of mutations in CP patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1432-0584
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47-52
pubmed:meshHeading
pubmed-meshheading:20697894-Adolescent, pubmed-meshheading:20697894-Adult, pubmed-meshheading:20697894-Aged, pubmed-meshheading:20697894-Antineoplastic Agents, pubmed-meshheading:20697894-Asian Continental Ancestry Group, pubmed-meshheading:20697894-DNA Mutational Analysis, pubmed-meshheading:20697894-Drug Resistance, Neoplasm, pubmed-meshheading:20697894-Female, pubmed-meshheading:20697894-Fusion Proteins, bcr-abl, pubmed-meshheading:20697894-Genes, abl, pubmed-meshheading:20697894-Humans, pubmed-meshheading:20697894-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:20697894-Male, pubmed-meshheading:20697894-Middle Aged, pubmed-meshheading:20697894-Phosphotransferases, pubmed-meshheading:20697894-Piperazines, pubmed-meshheading:20697894-Point Mutation, pubmed-meshheading:20697894-Protein Structure, Tertiary, pubmed-meshheading:20697894-Pyrimidines, pubmed-meshheading:20697894-Young Adult
pubmed:year
2011
pubmed:articleTitle
Characteristics of BCR-ABL kinase domain point mutations in Chinese imatinib-resistant chronic myeloid leukemia patients.
pubmed:affiliation
Institute of Hematology, People's Hospital of Peking University, 11 Xi-zhi-men South Street, Beijing, People's Republic of China, 100044.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't