FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2497163359> ?p ?o ?g. }

• W2497163359 abstract "Abstract Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, representing 31% of all tumors, and about 85% of children with ALL have B-cell ALL. Although the survival rate is approaching 90%, ALL remains the main cause of death from disease in children and young adults. The activity of histone deacetylases (HDAC) in childhood ALL is increased compared with that in normal peripheral blood mononuclear cells or bone marrow cells. Treatment of mice engrafted with T or B-ALL cells with HDAC inhibitor (HDACi) increases the acetylation of Histone 3 and Histone 4 and prolongs survival of these mice. <>Vorinostat (Suberoylamilide Hydroxamic Acid, SAHA) was the first HDACi approved by the FDA for the treatment of refractory cutaneous T-cell lymphoma. Currently, several clinical trials are being conducted to evaluate its effects on other cancers, including ALL. However, some patients are resistant to HDACi therapy, and concerns regarding toxic side effects of HDACi exist due to the roles of HDACs in multiple pathways. Therefore, identification of new therapeutic targets is required which could improve the efficacy of HDACi by reducing the dose of HDACi administered without compromising the treatment benefits but alleviating the side effects of HDACi. <>CBP/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)–rich tail 2 (CITED2) is a cytokine-inducible gene that plays various roles during mouse development and, in particular, is essential for normal hematopoiesis. While the role of CITED2 in the pathogenesis of leukemia is currently unclear, dysregulation of CITED2 has been implicated in various types of leukemia, including ALL, in which downregulation of CITED2 is frequently observed. In this study, we tested the hypothesis that CITED2 may enhance the sensitivity of human pediatric pre-B ALL cells to HDACi SAHA. <>SAHA treatment of NALM-6 and 697 cells (human pediatric pre-B ALL cell lines) significantly induced apoptosis and cell cycle arrest in a dose dependent manner. The protein level of CITED2 was not affected by SAHA treatment. Although overexpression of CITED2 alone only slightly increased apoptosis, it significantly enhanced apoptosis resulted from SAHA treatment in both NALM-6 (15.1% versus 39.2%) and 697 cells (9.4% versus 14.6%) as assessed by annexin V/Propidium Iodide double staining and flow cytometry analysis (Figure 1). Accordingly, compared with control (i.e. NALM-6 cells transduced with GFP), overexpression of CITED2 also greatly reduced mitochondrial membrane potential of NALM-6 cells caused by SAHA treatment. To explore the potential mechanisms underlying enhanced apoptosis by overexpression of CITED2 in NALM-6 cells treated with SAHA, we determined the levels of pro- and anti- apoptotic proteins by Western blot and real-time quantitative PCR. We found that SAHA treatment increased the levels of pro-apoptotic molecules Bak, Puma, and Noxa, and decreased the levels of anti-apoptotic molecule Bcl-xL and apoptosis inhibitors XIAP and survivin. Importantly, overexpression of CITED2 markedly increased the protein levels of pro-apoptotic molecules Bak and Bim. Furthermore, knockdown of Bim by shRNA significantly attenuated apoptosis in Cited2 overexpressing NALM-6 cells treated with SAHA. Taken together, these results suggest that modulation of the CITED2 activity may confer its cooperative effect with SAHA in pre-B ALL cells and warrant future evaluation of such a combination in inducing apoptosis of primary ALL cells. Disclosures: No relevant conflicts of interest to declare." @default.
• W2497163359 created "2016-08-23" @default.
• W2497163359 creator A5014586199 @default.
• W2497163359 creator A5033188972 @default.
• W2497163359 creator A5075756576 @default.
• W2497163359 date "2013-11-15" @default.
• W2497163359 modified "2023-09-27" @default.
• W2497163359 title "CITED2 Facilitates Apoptosis Induced By Histone Deacetylase Inhibitor SAHA In Human Pediatric Pre-B Acute Lymphoblastic Leukemia Cells" @default.
• W2497163359 doi "https://doi.org/10.1182/blood.v122.21.2913.2913" @default.
• W2497163359 hasPublicationYear "2013" @default.
• W2497163359 type Work @default.
• W2497163359 sameAs 2497163359 @default.
• W2497163359 citedByCount "0" @default.
• W2497163359 crossrefType "journal-article" @default.
• W2497163359 hasAuthorship W2497163359A5014586199 @default.
• W2497163359 hasAuthorship W2497163359A5033188972 @default.
• W2497163359 hasAuthorship W2497163359A5075756576 @default.
• W2497163359 hasConcept C104317684 @default.
• W2497163359 hasConcept C203014093 @default.
• W2497163359 hasConcept C2776202225 @default.
• W2497163359 hasConcept C2776262904 @default.
• W2497163359 hasConcept C2778305200 @default.
• W2497163359 hasConcept C2778461978 @default.
• W2497163359 hasConcept C2780007613 @default.
• W2497163359 hasConcept C2780225316 @default.
• W2497163359 hasConcept C502942594 @default.
• W2497163359 hasConcept C55493867 @default.
• W2497163359 hasConcept C64927066 @default.
• W2497163359 hasConcept C71924100 @default.
• W2497163359 hasConcept C86803240 @default.
• W2497163359 hasConceptScore W2497163359C104317684 @default.
• W2497163359 hasConceptScore W2497163359C203014093 @default.
• W2497163359 hasConceptScore W2497163359C2776202225 @default.
• W2497163359 hasConceptScore W2497163359C2776262904 @default.
• W2497163359 hasConceptScore W2497163359C2778305200 @default.
• W2497163359 hasConceptScore W2497163359C2778461978 @default.
• W2497163359 hasConceptScore W2497163359C2780007613 @default.
• W2497163359 hasConceptScore W2497163359C2780225316 @default.
• W2497163359 hasConceptScore W2497163359C502942594 @default.
• W2497163359 hasConceptScore W2497163359C55493867 @default.
• W2497163359 hasConceptScore W2497163359C64927066 @default.
• W2497163359 hasConceptScore W2497163359C71924100 @default.
• W2497163359 hasConceptScore W2497163359C86803240 @default.
• W2497163359 hasLocation W24971633591 @default.
• W2497163359 hasOpenAccess W2497163359 @default.
• W2497163359 hasPrimaryLocation W24971633591 @default.
• W2497163359 hasRelatedWork W1509902987 @default.
• W2497163359 hasRelatedWork W1971843137 @default.
• W2497163359 hasRelatedWork W2018172208 @default.
• W2497163359 hasRelatedWork W2066052727 @default.
• W2497163359 hasRelatedWork W2074981228 @default.
• W2497163359 hasRelatedWork W2086991127 @default.
• W2497163359 hasRelatedWork W2087407588 @default.
• W2497163359 hasRelatedWork W2112600117 @default.
• W2497163359 hasRelatedWork W2323767515 @default.
• W2497163359 hasRelatedWork W2463166538 @default.
• W2497163359 hasRelatedWork W2556070719 @default.
• W2497163359 hasRelatedWork W2556143404 @default.
• W2497163359 hasRelatedWork W2560357428 @default.
• W2497163359 hasRelatedWork W2561336479 @default.
• W2497163359 hasRelatedWork W2582730052 @default.
• W2497163359 hasRelatedWork W2586018824 @default.
• W2497163359 hasRelatedWork W2741244622 @default.
• W2497163359 hasRelatedWork W2976557502 @default.
• W2497163359 hasRelatedWork W2979569721 @default.
• W2497163359 hasRelatedWork W348581781 @default.
• W2497163359 isParatext "false" @default.
• W2497163359 isRetracted "false" @default.
• W2497163359 magId "2497163359" @default.
• W2497163359 workType "article" @default.