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
Dans Chinois
| WPRIM
| ID: wpr-302378
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.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Pharmacologie
/
Mutation ponctuelle
/
Résistance aux médicaments antinéoplasiques
/
DNA Glycosylases
/
Asiatiques
/
Inhibiteurs de protéines kinases
/
Uracil-DNA glycosidase
/
Leucémie-lymphome lymphoblastique à précurseurs B et T
/
Génétique
Limites du sujet:
Adolescent
/
Adulte
/
Femelle
/
Humains
/
Mâle
langue:
Chinois
Texte intégral:
Journal of Experimental Hematology
Année:
2014
Type:
Article
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