Abstract
This study aimed to investigate the effects of Twist1 on the drug resistance of chronic myeloid leukemia (CML) cells through the PI3K/AKT signaling pathway. K562 and KCL-22 cells were modeled for imatinib resistance, so as to analyze the effects of inhibiting Twist1 and the pathway on the therapeutic effect of imatinib on imatinib-resistant CML cells, and to find the mechanism of action of Twist1 on affecting the resistance. After the CML cells were successfully resistant to imatinib, Twist1 expression increased again in the cells and the PI3K/AKT signaling pathway was further activated. After the silence of the Twist1 expression, the imatinib-resistant CML cells were more sensitive to imatinib, and the PI3K/AKT signaling pathway was inhibited, and the expression level of p-AKT protein significantly reduced. According to further experiments, imatinib enhanced its inhibitory effect on the growth of the imatinib-resistant CML cells after the activation of the pathway was inhibited by an LY3023414 inhibitor. In conclusion, Twist1 and the PI3K/AKT signaling pathway are over-activated during the formation of the CML cells resistant to imatinib. The silence of Twist1 can reverse the resistance through the pathway.
Highlights
Chronic myeloid leukemia (CML) is an unusual type of bone marrow cancer
This study aimed to investigate the effects of Twist1 on the drug resistance of chronic myeloid leukemia (CML) cells through the PI3K/AKT signaling pathway
K562 and KCL-22 cells were modeled for imatinib resistance, so as to analyze the effects of inhibiting Twist1 and the pathway on the therapeutic effect of imatinib on imatinib-resistant CML cells, and to find the mechanism of action of Twist1 on affecting the resistance
Summary
Chronic myeloid leukemia (CML) is an unusual type of bone marrow cancer. CML increases the number of white blood cells. The term "chronic" leukemia suggests that cancer tends to progress gradually to acute types of leukemia. The term “myeloid” refers to the type of cells with this cancer. CML is a disease in which the bone marrow of many white blood cells develops. The incidence of the disease among people of different ages significantly varies. According to statistics in 20 EU countries, the incidence among people aged 20-29 years is 0.39/100,000 people, while that among people over 70 years old rapidly increases to 15.2/100,000 people [3]. The incidence of CML will further increase [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
