title: [Frequently ABL kinase domain G:C→A:T mutation and uracil DNA glycosylase abnormal expression in TKI-resistant acute lymphoblastic leukemia of Chinese population].
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→A:T, 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 G:C→A:T 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 G:C→A:T 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 G:C→A:T mutation.
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Hong-Jie
authors.initials: HJ
authors.lastname: Shen
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China. E-mail: szchenzx@263.net.
authors.forename: Zi-Xing
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Cen
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Qiao-Chen
authors.initials: QC
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Zi-Xuan
authors.initials: ZX
authors.lastname: Ding
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Su-Ning
authors.initials: SN
authors.lastname: Chen
authors.affiliation: Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Jiangsu Insitute of Hematology, The First Affiliate Hospital of Soochow University, Suzhou 215006, Jiansu Province, China.
authors.forename: Yong-Quan
authors.initials: YQ
authors.lastname: Xue
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051981:Uracil-DNA Glycosidase / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; C492570:CCNO protein, human; D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase