FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384665104> ?p ?o ?g. }

• W4384665104 abstract "Abstract Background DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia (AML) with Arg882His (R882H) as the hotspot mutation. It has been reported that DNMT3A mutation plays a key role in leukemogenesis through hypomethylation of some target genes associated with cell growth and differentiation. In this study, we investigated the function of DNMT3A R882H in the malignant progression of AML by regulating metabolic reprogramming. Methods Ultra-High Performance Liquid Chromatography–High Resolution Tandem Mass Spectrometry (UHPLC-HRMS/MS) was used to detect metabolites in the serum of mice harboring Dnmt3a R878H mutation and the wild-type Dnmt3a. Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq) and RNA sequencing (RNA-seq) were used to analyze the levels of DNA methylation and mRNA expression of genes in mouse Gr1 + bone marrow cells respectively. The TCGA and GO databases were used to analyze the differential genes between human samples carrying the DNMT3A R882 mutation and the wild-type DNMT3A. Co-immunoprecipitation and immunoblotting were used to illustrate the binding levels of Cyclins-CDKs and CDK inhibitors including CDKN1A and CDKN1B. Flow cytometry was used to analyze the cell differentiation, division, apoptosis and cell cycle. The effect of NAMPT inhibition on leukemia was evaluated by using in vivo fluorescence imaging in NOG mouse model bearing OCI-AML3 cells. Results DNMT3A mutation caused high expression of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the nicotinamide adenine dinucleotide (NAD) salvage synthetic pathway, through DNA hypomethylation, and finally led to abnormal nicotinamide (NAM) metabolism and NAD synthesis. The NAM-NAD metabolic abnormalities caused accelerated cell cycle progression. Inhibition of NAMPT can reduce the binding degree between Cyclins-CDKs, and increase the binding interaction of the CDK inhibitors with Cyclins-CDKs complexes. Moreover, cells with high expression of NAMPT were more sensitive to the NAMPT inhibitor FK866 with a lower IC50. The inhibition of NAMPT can remarkably extend the survival time of tumor-bearing mice and reduce the infiltration of tumor cells. Conclusions Taken together, our data showed that DNMT3A mutation caused NAMPT overexpression to induce the reprogramming of NAM-NAD metabolism and contribute to abnormal proliferation, which provided a potential direction for targeted therapy at the metabolic level in AML with DNMT3A mutation." @default.
• W4384665104 created "2023-07-20" @default.
• W4384665104 creator A5000797999 @default.
• W4384665104 creator A5007199414 @default.
• W4384665104 creator A5007214233 @default.
• W4384665104 creator A5030670891 @default.
• W4384665104 creator A5036526021 @default.
• W4384665104 creator A5058010200 @default.
• W4384665104 creator A5063865607 @default.
• W4384665104 date "2023-07-18" @default.
• W4384665104 modified "2023-10-14" @default.
• W4384665104 title "DNMT3A mutation promotes leukemia development through NAM-NAD metabolic reprogramming" @default.
• W4384665104 cites W2002583208 @default.
• W4384665104 cites W2049801905 @default.
• W4384665104 cites W2063441242 @default.
• W4384665104 cites W2134295414 @default.
• W4384665104 cites W2140929811 @default.
• W4384665104 cites W2325815501 @default.
• W4384665104 cites W2406277694 @default.
• W4384665104 cites W2531874824 @default.
• W4384665104 cites W2599841336 @default.
• W4384665104 cites W2611416498 @default.
• W4384665104 cites W2625742115 @default.
• W4384665104 cites W2791070352 @default.
• W4384665104 cites W2803357178 @default.
• W4384665104 cites W2804005168 @default.
• W4384665104 cites W2902301444 @default.
• W4384665104 cites W2914775802 @default.
• W4384665104 cites W2941157636 @default.
• W4384665104 cites W2943378083 @default.
• W4384665104 cites W2946593577 @default.
• W4384665104 cites W2962822924 @default.
• W4384665104 cites W2963684339 @default.
• W4384665104 cites W2969666399 @default.
• W4384665104 cites W2984175559 @default.
• W4384665104 cites W3006227213 @default.
• W4384665104 cites W3025899813 @default.
• W4384665104 cites W3079197556 @default.
• W4384665104 cites W3083662059 @default.
• W4384665104 cites W3112623251 @default.
• W4384665104 cites W3122921488 @default.
• W4384665104 cites W3138703087 @default.
• W4384665104 cites W3158011042 @default.
• W4384665104 cites W3158263555 @default.
• W4384665104 cites W3165193121 @default.
• W4384665104 cites W4200029042 @default.
• W4384665104 cites W4200065926 @default.
• W4384665104 cites W4206898324 @default.
• W4384665104 cites W4224212113 @default.
• W4384665104 cites W4282924424 @default.
• W4384665104 cites W4285588679 @default.
• W4384665104 cites W4296683167 @default.
• W4384665104 cites W4307968061 @default.
• W4384665104 cites W4309324122 @default.
• W4384665104 cites W4313429659 @default.
• W4384665104 cites W4315783817 @default.
• W4384665104 cites W4327715693 @default.
• W4384665104 cites W4367835018 @default.
• W4384665104 doi "https://doi.org/10.1186/s12967-023-04323-z" @default.
• W4384665104 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37464424" @default.
• W4384665104 hasPublicationYear "2023" @default.
• W4384665104 type Work @default.
• W4384665104 citedByCount "0" @default.
• W4384665104 crossrefType "journal-article" @default.
• W4384665104 hasAuthorship W4384665104A5000797999 @default.
• W4384665104 hasAuthorship W4384665104A5007199414 @default.
• W4384665104 hasAuthorship W4384665104A5007214233 @default.
• W4384665104 hasAuthorship W4384665104A5030670891 @default.
• W4384665104 hasAuthorship W4384665104A5036526021 @default.
• W4384665104 hasAuthorship W4384665104A5058010200 @default.
• W4384665104 hasAuthorship W4384665104A5063865607 @default.
• W4384665104 hasBestOaLocation W43846651041 @default.
• W4384665104 hasConcept C101762097 @default.
• W4384665104 hasConcept C104317684 @default.
• W4384665104 hasConcept C134320426 @default.
• W4384665104 hasConcept C150194340 @default.
• W4384665104 hasConcept C153911025 @default.
• W4384665104 hasConcept C181199279 @default.
• W4384665104 hasConcept C190727270 @default.
• W4384665104 hasConcept C2778729363 @default.
• W4384665104 hasConcept C2780391879 @default.
• W4384665104 hasConcept C29537977 @default.
• W4384665104 hasConcept C502942594 @default.
• W4384665104 hasConcept C55493867 @default.
• W4384665104 hasConcept C75520062 @default.
• W4384665104 hasConcept C86803240 @default.
• W4384665104 hasConceptScore W4384665104C101762097 @default.
• W4384665104 hasConceptScore W4384665104C104317684 @default.
• W4384665104 hasConceptScore W4384665104C134320426 @default.
• W4384665104 hasConceptScore W4384665104C150194340 @default.
• W4384665104 hasConceptScore W4384665104C153911025 @default.
• W4384665104 hasConceptScore W4384665104C181199279 @default.
• W4384665104 hasConceptScore W4384665104C190727270 @default.
• W4384665104 hasConceptScore W4384665104C2778729363 @default.
• W4384665104 hasConceptScore W4384665104C2780391879 @default.
• W4384665104 hasConceptScore W4384665104C29537977 @default.
• W4384665104 hasConceptScore W4384665104C502942594 @default.
• W4384665104 hasConceptScore W4384665104C55493867 @default.
• W4384665104 hasConceptScore W4384665104C75520062 @default.
• W4384665104 hasConceptScore W4384665104C86803240 @default.

• next