Document Detail


The quantitative level of T315I mutated BCR-ABL predicts for major molecular response to second-line nilotinib or dasatinib treatment in patients with chronic myeloid leukemia.
MedLine Citation:
PMID:  23065514     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The BCR-ABL T315I mutation causes resistance to imatinib, nilotinib and dasatinib in chronic myeloid leukemia. Forty BCR-ABL positive patients with imatinib resistance were analyzed for T315I mutated clones after six months on nilotinib or dasatinib treatment by quantitative allele-specific ligation polymerase chain reaction with a sensitivity of 0.05%. Ligation polymerase chain reaction revealed 10 patients with more than 10(-5) BCR-ABL(T315I%)/GUS (high levels), none of whom achieved major molecular response after 12 months, and a further 8 patients with 10(-5) or below BCR-ABL(T315I%)/GUS (low levels) who all achieved major molecular response (P<0.001). A second independent group showed molecular response in one of 12 patients with high levels and 5 of 8 patients with low levels (P=0.018). Combining the groups resulted in a sensitivity and specificity of 92.9% and 87.5%, respectively. We conclude that the quantitative level of mutant T315I allele is predictive of major molecular response at 12 months on second-line nilotinib or dasatinib treatment. www.clinicaltrials.gov: CT00109707, NCT00384228, CA180013, CA180005 CA180006.
Authors:
Thoralf Lange; Thomas Ernst; Franz X Gruber; Jacqueline Maier; Michael Cross; Martin C Müller; Dietger Niederwieser; Andreas Hochhaus; Markus Pfirrmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-12
Journal Detail:
Title:  Haematologica     Volume:  98     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-01     Completed Date:  2013-12-03     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  714-7     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00384228
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Antineoplastic Agents / therapeutic use*
Drug Resistance, Neoplasm / genetics
Female
Fusion Proteins, bcr-abl / genetics*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  genetics*,  pathology
Male
Middle Aged
Mutation*
Prognosis
Protein Kinase Inhibitors / therapeutic use
Pyrimidines / therapeutic use*
Thiazoles / therapeutic use*
Treatment Outcome
Chemical
Reg. No./Substance:
0/4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide; 0/Antineoplastic Agents; 0/Protein Kinase Inhibitors; 0/Pyrimidines; 0/Thiazoles; EC 2.7.10.2/Fusion Proteins, bcr-abl; RBZ1571X5H/dasatinib
Comments/Corrections
Comment In:
Haematologica. 2013 May;98(5):665-6   [PMID:  23633541 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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