کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10899298 | 1084359 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation Metabolic alterations and drug sensitivity of tyrosine kinase inhibitor resistant leukemia cells with a FLT3/ITD mutation](/preview/png/10899298.png)
چکیده انگلیسی
Internal tandem duplication (ITD) of the juxtamembrane region of FMS-like tyrosine kinase-3 (FLT3) receptor is a common type of mutation in adult acute myeloid leukemia (AML), and patient response to FLT3 inhibitors appears to be transient due to the emergence of drug resistance. We established two sorafenib-resistant cell lines carrying FLT3/ITD mutations, including the murine BaF3/ITD-R and human MV4-11-R cell lines. Gene expression profile analysis of the resistant and parental cells suggests that the highest ranked molecular and cellular functions of the differentially expressed genes are related to mitochondrial dysfunction. Both murine and human resistant cell lines display a longer doubling time, along with a significant inhibition of mitochondrial respiratory chain activity and substantial upregulation of glycolysis. The sorafenib-resistant cells exhibit increased expression of a majority of glycolytic enzymes, including hexokinase 2, which is also highly expressed in the mitochondrial fraction and is associated with resistance to apoptotic cell death. The sorafenib-resistant cells are collaterally sensitive to a number of glycolytic inhibitors including 2-deoxyglucose and 3-bromopyruvate propylester. Our study reveals a metabolic signature of sorafenib-resistant cells and suggests that glycolytic inhibition may override such resistance and warrant further clinical investigation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 377, Issue 2, 28 July 2016, Pages 149-157
Journal: Cancer Letters - Volume 377, Issue 2, 28 July 2016, Pages 149-157
نویسندگان
Amin Huang, Huai-Qiang Ju, Kaiyan Liu, Guilian Zhan, Daolu Liu, Shijun Wen, Guillermo Garcia-Manero, Peng Huang, Yumin Hu,