The change of nuclear LC3 distribution in acute myeloid leukemia cells

Guo, Weidong; Jin, Jie; Pan, Jiajia; Yao, Rongxing; Li, Xia; Huang, Xin; Ma, Zhixing; Huang, Sujuan; Yan, Xiao; Dong, Aishu

doi:10.1016/j.yexcr.2018.05.007

Cited by 6 publications

(14 citation statements)

References 28 publications

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“…pathway, the P53 pathway, and others. During analysis, SIRT1 was also found to be related to the AMPK pathway and autophagy pathway, consistent with findings from our previous study (23).…”

Section: Differential Expression Of Genes Across Experimental Conditisupporting

confidence: 90%

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia

et al. 2020

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Changes in histone H3 lysine 9 trimethylation (H3K9me3) may be related to the development of drug-resistant acute myeloid leukaemia (AML); insights into the network of H3K9me3 may improve patient prognosis. Patient data were derived from the Gene Expression Omnibus (GEO) database and data from AML cells treated with chidamide, a novel benzamide chemical class of histone deacetylase inhibitor (HDACi), in vitro were derived from ChIP-seq. Patients and AML cell data were analysed using GEO2R, GOseq, KOBAS, the STRING database and Cytoscape 3.5.1. We identified several genes related to the upregulation or downregulation of H3K9me3 in AML patients; some of these genes were related to apoptosis, autophagy, and the pathway of cell longevity. AML cells treated with chidamide in vitro showed the same gene changes. The protein interactions in the network did not have significantly more interactions than expected, suggesting the need for more research to identify these interactions. One compelling result from the protein interaction study was that sirtuin 1 (SIRT1) may have an indirect interaction with lysine-specific demethylase 4A (KDM4A). These results help explain alterations of H3K9me3 in AML that may direct further studies aimed at improving patient prognosis. These results may also provide a basis for chidamide as a treatment strategy for AML patients in the future.

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“…pathway, the P53 pathway, and others. During analysis, SIRT1 was also found to be related to the AMPK pathway and autophagy pathway, consistent with findings from our previous study (23).…”

Section: Differential Expression Of Genes Across Experimental Conditisupporting

confidence: 90%

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia

et al. 2020

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“…Autophagy is often reduced in human AML cells and the loss of key autophagy genes leads to leukemia initiation and progression in mouse models [91]. On the other hand, autophagy seems important for the pro-survival protection of AML cells, and exposure of the leukemic cells to antileukemic drugs (i.e., cytarabine, anthracyclines and sorafenib) seems to activate and increases autophagic flux and thereby allowing them to resist chemotherapy [92][93][94][95]. These different roles suggest that the effect of therapeutic targeting of autophagy in human AML will differ between patients, and this is also consistent with our present data.…”

Section: Discussionmentioning

confidence: 99%

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

Aasebø

Berven

Bartaula-Brevik

et al. 2020

Cancers

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Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies.

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“…Notably, and similar to CML, many studies in AML have shown another consistently critical role for autophagy with treatment implications: pro-survival protection of leukemic cells upon chemotherapy. For instance, it has been demonstrated that treatment of AML cells with cytarabine (AraC), anthracyclines, or sorafenib activates and increases autophagic flux in these cells, including LSCs, allowing them to resist chemotherapy [54,121,122]. However, in these cases, targeting of autophagy by genetic or pharmacological means, combined with chemotherapy, seems to hold great promise in developing more effective treatment strategies, as discussed later.…”

Section: Autophagy Plays Context-dependent Roles In Leukemia Initimentioning

confidence: 99%

Current Outlook on Autophagy in Human Leukemia: Foe in Cancer Stem Cells and Drug Resistance, Friend in New Therapeutic Interventions

Rothe

Porter

Jiang

2019

IJMS

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Autophagy is an evolutionarily conserved cellular recycling process in cell homeostasis and stress adaptation. It confers protection and promotes survival in response to metabolic/environmental stress, and is upregulated in response to nutrient deprivation, hypoxia, and chemotherapies. Autophagy is also known to sustain malignant cell growth and contributes to cancer stem cell survival when challenged by cytotoxic and/or targeted therapies, a potential mechanism of disease persistence and drug resistance that has gathered momentum. However, different types of human leukemia utilize autophagy in complex, context-specific manners, and the molecular and cellular mechanisms underlying this process involve multiple protein networks that will be discussed in this review. There is mounting preclinical evidence that targeting autophagy can enhance the efficacy of cancer therapies. Chloroquine and other lysosomal inhibitors have spurred initiation of clinical trials and demonstrated that inhibition of autophagy restores chemosensitivity of anticancer drugs, but with limited autophagy-dependent effects. Intriguingly, several autophagy-specific inhibitors, with better therapeutic indexes and lower toxicity, have been developed. Promising preclinical studies with novel combination approaches as well as potential challenges to effectively eradicate drug-resistant cells, particularly cancer stem cells, in human leukemia are also detailed in this review.

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The change of nuclear LC3 distribution in acute myeloid leukemia cells

Cited by 6 publications

References 28 publications

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia

Bioinformatics analysis of the network of histone H3 lysine 9 trimethylation in acute myeloid leukaemia

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

Current Outlook on Autophagy in Human Leukemia: Foe in Cancer Stem Cells and Drug Resistance, Friend in New Therapeutic Interventions

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