Document Detail


GSTT1 copy number gain is a poor predictive marker for escalated-dose imatinib treatment in chronic myeloid leukemia: genetic predictive marker found using array comparative genomic hybridization.
MedLine Citation:
PMID:  21156236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In a study population of 45 patients who were previously enrolled in an imatinib dose escalation trial, genome-wide screening for regions of genetic gains and losses was performed using array comparative genomic hybridization (aCGH). Early molecular response (EMR), defined as >50% reduction in the ratio of BCR-ABL1 to ABL1 within 6 months after dose escalation, was a major endpoint for analysis. After aCGH analysis, copy number change of four genes was investigated in 52 patients as a validation. Copy number gain in 16p11.2 was more frequently observed in patients with EMR than in patients who failed to achieve EMR (P = 0.034). A tendency for increased copy number in 22q11.23 in patients without EMR and for decreased copy number in 17q12 in patients with EMR was observed (P = 0.072 and P = 0.070, respectively). For GSTT1, in 22q11.23, copy number gain was observed in patients without EMR (P = 0.035). GSTT1 copy number gain was related to short time to treatment failure (TTFx) in patients without BCR-ABL1 mutations (P = 0.007). In multivariate analysis, GSTT1 copy number gain was an independent predictive factor for short TTFx (P = 0.020). We conclude that chromosome regions 16p11.2, 22q11.23, and 17q12 are potential locations related to response in imatinib dose escalation therapy for CML. GSTT1 copy number gain is a genetic change affecting outcome in this setting.
Authors:
Youngil Koh; Dae-Young Kim; Sung-Hyo Park; Seung-Hyun Jung; Eunkyung Park; Hyeoung-Joon Kim; Sang Kyun Sohn; Young Don Joo; Seok Jin Kim; Ho-Jin Shin; Sung-Hyun Kim; Hong Suk Song; Jooseop Chung; Inho Kim; Sung-Soo Yoon; Byoung Kook Kim; Seung-Hun Shin; Yeun-Jun Chung; Seonyang Park
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer genetics and cytogenetics     Volume:  203     ISSN:  1873-4456     ISO Abbreviation:  Cancer Genet. Cytogenet.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-15     Completed Date:  2011-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909240     Medline TA:  Cancer Genet Cytogenet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  215-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Department of Internal Medicine, Seoul National University Hospital, Seoul National University, 101 Daehagro, Jongno-Ku, Seoul 110-744, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Antineoplastic Agents / pharmacology*
Comparative Genomic Hybridization*
Female
Fusion Proteins, bcr-abl / genetics
Gene Dosage
Gene Expression Regulation, Leukemic*
Genetic Markers*
Glutathione Transferase / genetics*
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
Male
Middle Aged
Piperazines / pharmacology*
Predictive Value of Tests
Pyrimidines / pharmacology*
Tumor Markers, Biological*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Genetic Markers; 0/Piperazines; 0/Pyrimidines; 0/Tumor Markers, Biological; 152459-95-5/imatinib; EC 2.5.1.-/glutathione S-transferase T1; EC 2.5.1.18/Glutathione Transferase

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


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