Frequently ABL kinase domain G:C→A:T mutation and uracil DNA glycosylase abnormal expression in TKI-resistant acute lymphoblastic leukemia of Chinese population / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 889-893, 2014.
Article
in Chinese
| WPRIM (Western Pacific)
| ID: wpr-302378
Responsible library:
WPRO
ABSTRACT
Most Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) patients often show rapid recurrence and development of ABL kinase domain (KD) mutation after tyrosine kinase inhibitor (TKI) treatment. To further investigate the mechanism of Ph(+) ALL fast relapse after TKI treatment, ABL KD mutation in 35 Chinese Ph(+) ALL with TKI resistance was detected by direct sequencing. The results showed that 77.1% (27/35) Ph(+) ALL patients with TKI resistance had ABL KD mutation and 55.6% (15/27) Ph(+) ALL patients with ABL KD mutation had T315I. Interestingly, 77.8% (21/27) Ph(+)ALL showed ABL mutation G C→AT, including T315I, E255K and E459K. Furthermore, all the Ph(+) ALL patients with two or more ABL KD mutations collaborated with complex chromosome abnormality and all the TKI-resistant Ph(+) ALL patients, whose karyotype progressed from simple t (9;22) into complex, developed ABL KD mutation. Moreover, the expression level of uracil-DNA glycosylase UNG2, which inhibits GC→AT transition in genomic DNA, decreased in Ph(+) ALL with TKI-resistance compared to that in newly diagnosis Ph(+) ALL. It is concluded that there is a high frequent ABL KD GC→AT mutation and a high genomic instability in Chinese TKI-resistant Ph(+) ALL. In addition, the decreased UNG2 expression in TKI-resistant Ph(+) ALL probably contributes to their high rate of ABL KD GC→AT mutation.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Point Mutation
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Drug Resistance, Neoplasm
/
DNA Glycosylases
/
Asian People
/
Protein Kinase Inhibitors
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Uracil-DNA Glycosidase
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Genetics
Limits:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Language:
Chinese
Journal:
Journal of Experimental Hematology
Year:
2014
Document type:
Article