Frequently ABL kinase domain G:C→A:T mutation and uracil DNA glycosylase abnormal expression in TKI-resistant acute lymphoblastic leukemia of Chinese population

• Published in: Zhongguo shi yan xue ye xue za zhi Vol. 22; no. 4; p. 889
• Main Authors: Shen, Hong-Jie, Chen, Zi-Xing, He, Jun, Cen, Jian-Nong, Qiu, Qiao-Chen, Ding, Zi-Xuan, Yao, Li, Chen, Yan, Chen, Su-Ning, Xue, Yong-Quan
• Format: Journal Article
• Language: Chinese
• Published: China 01.08.2014
• Subjects: Adolescent; Adult; Asian Continental Ancestry Group - genetics; DNA Glycosylases - genetics; Drug Resistance, Neoplasm - genetics; Female; Humans; Male; Middle Aged; Point Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Protein Kinase Inhibitors - pharmacology; Uracil-DNA Glycosidase - genetics
• ISSN: 1009-2137
• DOI: 10.7534/j.issn.1009-2137.2014.04.002

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 gen