Linked Life Data

19589924

Source:http://linkedlifedata.com/resource/pubmed/id/19589924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-9-4
pubmed:abstractText
Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) developed to overcome imatinib resistance in Philadelphia-positive leukemias. To assess how Bcr-Abl kinase domain mutation status evolves during sequential therapy with these TKIs and which mutations may further develop and impair their efficacy, we monitored the mutation status of 95 imatinib-resistant patients before and during treatment with dasatinib and/or nilotinib as second or third TKI. We found that 83% of cases of relapse after an initial response are associated with emergence of newly acquired mutations. However, the spectra of mutants conferring resistance to dasatinib or nilotinib are small and nonoverlapping, except for T315I. Patients already harboring mutations had higher likelihood of relapse associated with development of further mutations compared with patients who did not harbor mutations (23 of 51 vs 8 of 44, respectively, for patients who relapsed on second TKI; 13 of 20 vs 1 of 6, respectively, for patients who relapsed on third TKI).
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
2168-71
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19589924-Adolescent, pubmed-meshheading:19589924-Adult, pubmed-meshheading:19589924-Aged, pubmed-meshheading:19589924-Drug Resistance, Neoplasm, pubmed-meshheading:19589924-Female, pubmed-meshheading:19589924-Fusion Proteins, bcr-abl, pubmed-meshheading:19589924-Humans, pubmed-meshheading:19589924-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:19589924-Male, pubmed-meshheading:19589924-Middle Aged, pubmed-meshheading:19589924-Mutation, pubmed-meshheading:19589924-Piperazines, pubmed-meshheading:19589924-Precursor Cell Lymphoblastic Leukemia-Lymphoma, pubmed-meshheading:19589924-Protein Kinase Inhibitors, pubmed-meshheading:19589924-Protein-Tyrosine Kinases, pubmed-meshheading:19589924-Pyrimidines, pubmed-meshheading:19589924-Recurrence, pubmed-meshheading:19589924-Thiazoles
pubmed:year
2009
pubmed:articleTitle
Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors.
pubmed:affiliation
Department of Hematology and Oncological Sciences L e A Seràgnoli, University of Bologna, Bologna, Italy.
pubmed:publicationType
Journal Article, Comparative Study, Multicenter Study