Identification of Survival-Related Genes in Acute Myeloid Leukemia (AML) Based on Cytogenetically Normal AML Samples Using Weighted Gene Coexpression Network Analysis

Chen, Tingting; Zhang, Juan; Wang, Yinying; Zhou, Hebing

doi:10.1155/2022/5423694

Cited by 4 publications

(5 citation statements)

References 71 publications

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“…Network analysis of various molecular and regulatory factors [49,50] is a strong and widely used approach for exploring the underlying mechanisms of any disease. It has not only been used in AML research [51][52][53] but also for several other diseases and physiological conditions [54][55][56]. In the current study, we constructed protein-protein interaction network and revealed the close relationships among the m5C regulators.…”

Section: Discussionmentioning

confidence: 90%

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia

Ding,

Bajpai,

et al. 2024

Aging

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Acute myeloid leukemia (AML) is a highly heterogeneous malignant disease of the blood cell. The current therapies for AML are unsatisfactory and the molecular mechanisms underlying AML are unclear. 5-methylcytosine (m5C) is an important posttranscriptional modification of mRNA, and is involved in the regulation of mRNA stability, translation, and other aspects of RNA metabolism. However, based on our knowledge of published literature, the role of the m5C regulators has not been explored in AML till date. In this study, we clarified the expression and gene variants of m5C regulators in AML and found that most m5C regulators were differentially expressed and correlated with disease prognosis. We also found that the methylation status of certain m5C regulators (e.g., DNMT3A , DNMT3B ) affects the survival of AML patients. Two m5C modification subtypes, and high- and low-risk subgroups identified based on the expression of m5C regulators showed significant differences in the prognosis as well as immune cell infiltration. In addition, most of the m5C regulators were found to be correlated with miRNA expression in AML, as well as IC50 values of many drugs. The miRNA and GSVA analysis were used to identify the different miRNAs and KEGG or hallmark pathways between high- and low-risk subgroups. We also built a prognostic model based on m5C regulators, which was validated by two GSE databases. To verify the reliability of our analysis and conclusions, qPCR was used to identify the expressions of m5C regulators between normal and AML. In summary, we comprehensively explored the molecular characteristics of m5C regulators and built a prognostic model in AML. We proposed new mechanistic insights into the role of m5C in multiple databases and clinical data, which may pave novel ways for the development of therapeutic strategies.

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Section: Discussionmentioning

confidence: 90%

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia

Ding,

Bajpai,

et al. 2024

Aging

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“…First, transferrin receptor levels possibly reflect differences in iron metabolism that are important for chemosensitivity [94,95], extracellular mediator release and non-relapse survival after intensive therapy [96][97][98][99]. Second, Chitinase 3-like level is associated with survival for AML patients receiving intensive therapy [100,101]; cellular expression or systemic levels of the soluble form may function as markers of susceptibility to V-ATPase inhibition. Third, the secreted protein C type lectin domain containing 11A functions as a hematopoietic growth factor and high expression is associated with prognosis in AML [102,103].…”

Section: Discussionmentioning

confidence: 99%

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

Bartaula-Brevik,

Leitch,

Hernandez-Valladares

et al. 2023

JCM

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Vacuolar ATPase (V-ATPase) is regarded as a possible target in cancer treatment. It is expressed in primary acute myeloid leukemia cells (AML), but the expression varies between patients and is highest for patients with a favorable prognosis after intensive chemotherapy. We therefore investigated the functional effects of two V-ATPase inhibitors (bafilomycin A1, concanamycin A) for primary AML cells derived from 80 consecutive patients. The V-ATPase inhibitors showed dose-dependent antiproliferative and proapoptotic effects that varied considerably between patients. A proteomic comparison of primary AML cells showing weak versus strong antiproliferative effects of V-ATPase inhibition showed a differential expression of proteins involved in intracellular transport/cytoskeleton functions, and an equivalent phosphoproteomic comparison showed a differential expression of proteins that regulate RNA processing/function together with increased activity of casein kinase 2. Patients with secondary AML, i.e., a heterogeneous subset with generally adverse prognosis and previous cytotoxic therapy, myeloproliferative neoplasia or myelodysplastic syndrome, were characterized by a strong antiproliferative effect of V-ATPase inhibition and also by a specific mRNA expression profile of V-ATPase interactome proteins. Furthermore, the V-ATPase inhibition altered the constitutive extracellular release of several soluble mediators (e.g., chemokines, interleukins, proteases, protease inhibitors), and increased mediator levels in the presence of AML-supporting bone marrow mesenchymal stem cells was then observed, especially for patients with secondary AML. Finally, animal studies suggested that the V-ATPase inhibitor bafilomycin had limited toxicity, even when combined with cytarabine. To conclude, V-ATPase inhibition has antileukemic effects in AML, but this effect varies between patients.

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“…At the same time, the expression level of GPR84 was significantly related to the survival time of AML patients. 171 , 172 Mechanistically, GPR84 overexpression induces activation of the β-catenin transcriptional cofactors Tcf7l2 and c-Fos as well as genomes associated with Wnt signaling. 173 GPR84 antagonists have been evaluated in clinical trials to treat ulcerative colitis, idiopathic pulmonary fibrosis, and nonalcoholic steatohepatitis.…”

Section: Metabolite Sensing and Epigenetic Regulation Of Fatty Acid M...mentioning

confidence: 99%

Signaling pathways in cancer metabolism: mechanisms and therapeutic targets

You

Xie

Zhang

et al. 2023

Sig Transduct Target Ther

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A wide spectrum of metabolites (mainly, the three major nutrients and their derivatives) can be sensed by specific sensors, then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics, which is called metabolite sensing. Life body regulates metabolism, immunity, and inflammation by metabolite sensing, coordinating the pathophysiology of the host to achieve balance with the external environment. Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell, including cell proliferation, migration, invasion, angiogenesis, etc. Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer, thus forming a vicious circle. At the same time, exogenous metabolites can also affect the biological behavior of tumors. Here, we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives, as well as their abnormalities in the development of various cancers, and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.

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Identification of Survival-Related Genes in Acute Myeloid Leukemia (AML) Based on Cytogenetically Normal AML Samples Using Weighted Gene Coexpression Network Analysis

Cited by 4 publications

References 71 publications

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia

5-methylcytosine RNA modification regulators-based patterns and features of immune microenvironment in acute myeloid leukemia

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

Signaling pathways in cancer metabolism: mechanisms and therapeutic targets

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