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10.1038/nm.4399 http://scihub22266oqcxt.onion/10.1038/nm.4399 C5657469!5657469!28920959     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Med 2017 ; 23 (10): 1234-40 Nephropedia Template TP {{tp|p=28920959|t=2017. Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemic stem cells |pdf=|usr=}}{{28920959}} gab.com Text Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemic stem cells JO: Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28920959 #FOAvip Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second/third generation c-Abl specific tyrosine kinase inhibitors (TKIs) has significantly extended patient survival1. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs)2?4. Therefore, targeting minimal residual disease, to prevent acquired resistance and/or disease relapse requires identification of novel LSC-selective target(s) that can be exploited therapeutically5,6. Given that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner7, we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34+ and CD34+CD38-) and differentiated (CD34-) patient derived CML cells, and compared their signature with that of normal counterparts. Combining stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination-treatment of imatinib with tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs, both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong indication for investigating the employment of TKIs in combination with tigecycline to treat CML patients with minimal residual disease. Twit Text FOAVip Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemic stem cells ????Nat Med http://www.kidney.de/pget.php?&tw=1&pmid=28920959 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28920959 #FOAvip English Wikipedia <ref>{{Cite pmid|28920959}}</ref> Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemic stem cells #MMPMID28920959 Kuntz EM; Baquero P; Michie AM; Dunn K; Tardito S; Holyoake TL; Helgason GV; Gottlieb E Nat Med 2017[Oct]; 23 (10): 1234-40 PMID28920959show ga Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second/third generation c-Abl specific tyrosine kinase inhibitors (TKIs) has significantly extended patient survival1. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs)2?4. Therefore, targeting minimal residual disease, to prevent acquired resistance and/or disease relapse requires identification of novel LSC-selective target(s) that can be exploited therapeutically5,6. Given that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner7, we searched for such vulnerabilities in CML LSCs. We performed metabolic analyses on both stem cell-enriched (CD34+ and CD34+CD38-) and differentiated (CD34-) patient derived CML cells, and compared their signature with that of normal counterparts. Combining stable isotope-assisted metabolomics with functional assays, we demonstrate that primitive CML cells rely on upregulated oxidative metabolism for their survival. We also show that combination-treatment of imatinib with tigecycline, an antibiotic that inhibits mitochondrial protein translation, selectively eradicates CML LSCs, both in vitro and in a xenotransplantation model of human CML. Our findings provide a strong indication for investigating the employment of TKIs in combination with tigecycline to treat CML patients with minimal residual disease. äTargeting mitochondrial oxidative phosphorylation eradicates therapy-r(epmc).pdf DeepDyve Pubget Overpricing