2021
DOI: 10.1038/s41375-021-01315-0
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Metabolic alterations mediated by STAT3 promotes drug persistence in CML

Abstract: Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of drug persistence in LSCs are incompletely understood, which is the primary focus of this study. We integrated proteomics, transcriptomics, and metabolomics to determine the contribution of STAT3 in promoting metabolic changes in tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Proteomic and transcription… Show more

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Cited by 29 publications
(39 citation statements)
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“…STAT3 activation was found to be correlated with TKI resistance in CML [ 74 ]. Recently, transcriptome and reverse-phase protein arrays with a STRING analysis of differentially active proteins within TKI-persistent K562 cells revealed that STAT3 and AKT1 are central nodes [ 75 ]. We therefore further verified the involvement of the JAK2/STAT3 pathway in 8-OHD-treated K562 cells by Western blotting.…”
Section: Resultsmentioning
confidence: 99%
“…STAT3 activation was found to be correlated with TKI resistance in CML [ 74 ]. Recently, transcriptome and reverse-phase protein arrays with a STRING analysis of differentially active proteins within TKI-persistent K562 cells revealed that STAT3 and AKT1 are central nodes [ 75 ]. We therefore further verified the involvement of the JAK2/STAT3 pathway in 8-OHD-treated K562 cells by Western blotting.…”
Section: Resultsmentioning
confidence: 99%
“…One of the effects of the STAT3 activation is the downregulation of PTEN ( 36 ). Indeed, some authors have observed that activation of STAT3/Akt/MAP2K and PKM2/glycolysis are relevant in drug-resistant cells ( 35 , 37 ). In addition to these cell intrinsic pathways, it has more recently become clear that cell extrinsic events involving EVs are important in events leading to therapy resistance.…”
Section: Evs In Cancer Therapy Resistance Induced By Hypoxia and Glyc...mentioning
confidence: 99%
“…AMPK regulates energy homeostasis and leads to glucose and fatty acid uptake upon activation. And in the case of BCR-ABL-independent TKI resistance, glycolytic genes are upregulated along with increased glucose uptake, lactate production, and reduced oxygen consumption ( 50 , 57 59 ). Although, this metabolic phenotype is partly similar to normal HSCs, the difference between HSCs and resistant CML LSCs is the dependency on the glycolytic pathway.…”
Section: Metabolism In Myeloid Leukemiamentioning
confidence: 99%
“…Although, this metabolic phenotype is partly similar to normal HSCs, the difference between HSCs and resistant CML LSCs is the dependency on the glycolytic pathway. Inhibition of PKM2 and LDHA, important enzymes for aerobic glycolysis, reduces disease progression and improves survival of CML mice, without impacting the surrounding HSCs ( 4 , 59 , 60 ). On the other hand, in advanced blast crisis CML, the stem cells have increased branched-chain amino acid metabolism ( 61 ).…”
Section: Metabolism In Myeloid Leukemiamentioning
confidence: 99%
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