2020
DOI: 10.1101/2020.09.21.305714
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Abstract: Long-term treatment with tyrosine kinase inhibitors (TKI) represents an effective treatment for chronic myeloid leukemia (CML) and discontinuation of TKI therapy is now proposed to patient with deep molecular responses. However, evidence demonstrating that TKI are unable to fully eradicate dormant leukemic stem cells indicate that new therapeutic strategies are needed to prevent molecular relapses. We investigated the metabolic pathways responsible for CML surviving to Imatinib exposure and its potential thera… Show more

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Cited by 2 publications
(3 citation statements)
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“…Other researches have demonstrated that this is indeed the case. Anne Trinh et al found that, after the treatment of IM, survived CML cells can continue to consume glutamine to create alphaKetoGlutarate, a TCA intermediate, that keeps the state of high mitochondrial oxidative metabolism (94). After that, they found that the combination of Kidrolase (an FDAapproved drug of L-asparaginase) and IM can deplete extracellular glutamine and therefore restrict mitochondrial metabolism.…”
Section: Glutaminementioning
confidence: 99%
See 1 more Smart Citation
“…Other researches have demonstrated that this is indeed the case. Anne Trinh et al found that, after the treatment of IM, survived CML cells can continue to consume glutamine to create alphaKetoGlutarate, a TCA intermediate, that keeps the state of high mitochondrial oxidative metabolism (94). After that, they found that the combination of Kidrolase (an FDAapproved drug of L-asparaginase) and IM can deplete extracellular glutamine and therefore restrict mitochondrial metabolism.…”
Section: Glutaminementioning
confidence: 99%
“…Furthermore, TKIs are unable to eradicate the leukemia stem cells (LSCs) and/or progenitor cells that could cause relapses (95). In order to kill LSCs, Anne Trinh et al also provided evidence that both glycolysis and glutamine-dependent mitochondrial metabolism required to be impaired (94). To prevent recurrence and achieve a longer OS of children, it may be an interesting therapeutic approach to eradicate LSCs by combining TKI and mitochondrial inhibitors.…”
Section: Glutaminementioning
confidence: 99%
“…Asparaginases have been shown to deplete the extracellular medium not only of asparagine but also of glutamine and therefore affect mitochondrial metabolism. 11 Glutamine depletion is able to overcome BCL2-mediated resistance to apoptosis. VEN not only induces apoptosis through BCL2 inhibition but also modulates mitochondrial metabolism, possibly in leukaemia stem cells.…”
mentioning
confidence: 99%