Linked Life Data

19567878

Source:http://linkedlifedata.com/resource/pubmed/id/19567878

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-9-4
pubmed:abstractText
Secondary imatinib resistance in chronic myeloid leukemia (CML) is associated in approximately 50% of cases with mutations in the BCR-ABL kinase domain, necessitating switch to one of several new tyrosine kinase inhibitors (TKIs) that act differentially on mutated BCR-ABL. We assess here whether scoring mutation based on in vitro inhibitory concentration of each TKI-mutation pair can predict long-term clinical outcome. Among 169 patients with CML after imatinib failure, mutations were detected before TKI switch in 41 (48%) treated with dasatinib and 45 (52%) treated with nilotinib. Inhibitory concentration values for each TKI-mutation pair were stratified into high (n = 42), intermediate (n = 25), low (T315I, n = 9), or unknown sensitivity (n = 10). Hematologic and cytogenetic response rates were similar for patients with or without mutations. For patients in chronic phase, hematologic and cytogenetic responses correlated with mutation score; tumors with low and intermediate scores had lower response rates than those with highly sensitive mutations, and worse event-free and overall survival. These correlations with overall survival were not seen for advanced phases. Mutation scoring can predict outcome in CML-chronic phase with imatinib failure treated with second-generation TKIs and can help in therapy selection. More complex prognostic models will be required for advanced stages of disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
114
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2037-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19567878-Adolescent, pubmed-meshheading:19567878-Adult, pubmed-meshheading:19567878-Age Factors, pubmed-meshheading:19567878-Aged, pubmed-meshheading:19567878-Aged, 80 and over, pubmed-meshheading:19567878-Disease-Free Survival, pubmed-meshheading:19567878-Drug Resistance, Neoplasm, pubmed-meshheading:19567878-Female, pubmed-meshheading:19567878-Fusion Proteins, bcr-abl, pubmed-meshheading:19567878-Hospitals, Public, pubmed-meshheading:19567878-Humans, pubmed-meshheading:19567878-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:19567878-Life Expectancy, pubmed-meshheading:19567878-Male, pubmed-meshheading:19567878-Middle Aged, pubmed-meshheading:19567878-Mutation, pubmed-meshheading:19567878-Piperazines, pubmed-meshheading:19567878-Protein Kinase Inhibitors, pubmed-meshheading:19567878-Protein Structure, Tertiary, pubmed-meshheading:19567878-Protein-Tyrosine Kinases, pubmed-meshheading:19567878-Pyrimidines, pubmed-meshheading:19567878-Retrospective Studies, pubmed-meshheading:19567878-Spain, pubmed-meshheading:19567878-Survival Rate, pubmed-meshheading:19567878-Thiazoles
pubmed:year
2009
pubmed:articleTitle
Long-term outcome of patients with chronic myeloid leukemia treated with second-generation tyrosine kinase inhibitors after imatinib failure is predicted by the in vitro sensitivity of BCR-ABL kinase domain mutations.
pubmed:affiliation
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
pubmed:publicationType
Journal Article