Metabolic assessment of a novel chronic myelogenous leukemic cell line and an imatinib resistant subline by H NMR spectroscopy.
Metabolic assessment of a novel chronic myelogenous leukemic cell line and an imatinib resistant subline by H NMR spectroscopy.
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DOI：
10.1007/s11306-010-0204-0
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发表时间：
2010-09
期刊：
影响因子：
3.6
通讯作者：
Macdonald, Jeffrey M.
中科院分区：
文献类型：
--
作者：
Dewar, Brian J.;Keshari, Kayvan;Jeffries, Rex;Dzeja, Petras;Graves, Lee M.;Macdonald, Jeffrey M.
这项研究的目的是检测一种新的慢性粒细胞白血病(CML)细胞系MYL和亚克隆MYL-R之间的代谢差异，MYL-R对靶向BCR-Abl酪氨酸激酶抑制剂伊马替尼表现出增强的抵抗力。对每种细胞类型的细胞提取液和条件培养液进行核磁共振氢谱分析。使用主成分分析(PCA)和特定代谢物鉴定和定量来检验不同细胞类型之间的代谢差异。与MYL-R细胞相比，MYL细胞表现出更强的葡萄糖清除能力，糖酵解最终产物乳酸和丙氨酸的产量有显著差异。有趣的是，与MYL细胞相比，MYL-R细胞内总肌酸池(肌酸+磷酸肌酸)显著增加。我们通过体内31P核磁共振波谱和随后的萃取物的高效液相分析，进一步证明了MYL-R细胞通过灌流的海藻酸盐包裹的MYL-R细胞和MYL细胞的非侵入性监测将肌酸转化为磷酸肌酸。我们的数据显示，耐药细胞和敏感细胞的代谢产物谱有明显的差异，最大的差异是伊马替尼耐药的Myl-R细胞中肌酸代谢产物的升高。
The goal of this study was to examine metabolic differences between a novel chronic myelogenous leukemic (CML) cell line, MyL, and a sub-clone, MyL-R, which displays enhanced resistance to the targeted Bcr-Abl tyrosine kinase inhibitor imatinib. 1H nuclear magnetic resonance (NMR) spectroscopy was carried out on cell extracts and conditioned media from each cell type. Both principal component analysis (PCA) and specific metabolite identification and quantification were used to examine metabolic differences between the cell types. MyL cells showed enhanced glucose removal from the media compared to MyL-R cells with significant differences in production rates of the glycolytic end-products, lactate and alanine. Interestingly, the total intracellular creatine pool (creatine + phosphocreatine) was significantly elevated in MyL-R compared to MyL cells. We further demonstrated that the MyL-R cells converted the creatine to phosphocreatine using non-invasive monitoring of perfused alginate-encapsulated MyL-R and MyL cells by in vivo 31P NMR spectroscopy and subsequent HPLC analysis of extracts. Our data demonstrated a clear difference in the metabolite profiles of drug-resistant and sensitive cells, with the biggest difference being an elevation of creatine metabolites in the imatinib-resistant MyL-R cells.
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影响因子：
8.8
作者：
Klawitter, J.;Anderson, N.;Klawitter, J.;Christians, U.;Leibfritz, D.;Eckhardt, S. G.;Serkova, N. J.
通讯作者：
Serkova, N. J.
影响因子：
7.3
作者：
Klawitter, Jelena;Kominsky, Douglas J.;Serkova, Natalie J.
通讯作者：
Serkova, Natalie J.
影响因子：
3.3
作者：
Keshari, Kayvan R.;Kurhanewicz, John;Jeffries, Rex E.;Wilson, David M.;Dewar, Brian J.;Van Criekinge, Mark;Zierhut, Matthew;Vigneron, Daniel B.;Macdonald, Jeffrey M.
通讯作者：
Macdonald, Jeffrey M.
影响因子：
11.5
作者：
Kominsky, Douglas J.;Klawitter, Jelena;Serkova, Natalie J.
通讯作者：
Serkova, Natalie J.
影响因子：
2.7
作者：
Franks, SE;Smith, MR;Brown, TR
通讯作者：
Brown, TR