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

Authors
Youngil KohDae-Young KimSung-Hyo ParkSeung-Hyun JungEunkyung ParkHyeoung-Joon KimSang Kyun SohnYoung Don JooSeok Jin KimHo-Jin ShinSung-Hyun KimHong Suk SongJooseop ChungInho KimSung-Soo YoonByoung Kook KimSeung-Hun ShinYeun-Jun ChungSeonyang Park
Department
Dept. of Internal Medicine (내과학)
Issue Date
2010
Citation
Cancer Genetics and Cytogenetics, Vol.203(2) : 215-221, 2010
ISSN
0165-4608
Abstract
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.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35305
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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Full Text
https://www.sciencedirect.com/science/article/pii/S0165460810004851?via%3Dihub
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