FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2556353357> ?p ?o ?g. }

• W2556353357 abstract "Abstract Abstract 4061 Multiple myeloma (MM) is a plasma cell malignancy presently incurable with heterogeneity in molecular abnormalities and treatment response. While the importance of Mcl-1 in maintaining survival of Human myeloma cell lines (HMCLs) has been well documented we recently identified a sub-group of HMCLs that highly expressed Bcl-2. This finding prompted us to investigate the sensitivity of HMCLs to ABT-737, a cell-permeant compound that binds with high affinity to Bcl-2 and antagonizes its anti-apoptotic function. The effect of ABT-737 on myeloma cell viability was assessed by APO2.7-PE staining on a large panel of HMCLs (n=26) representative of Multiple Myeloma molecular heterogeneity. We found 7 HMCLs highly sensitive to ABT-737 with an EC50 ranging from 7±0.4nM to 150±7.5nM. Myeloma cell death induced by ABT-737 occurred as early as 4 hours after treatment and led to Bax and Bak activation. While all these sensitive cell lines expressed a high level of Bcl-2, only Bcl-2/Mcl-1 gene expression ratio allowed the discrimination of highly ABT-737 sensitive from resistant HMCLs. High sensitivity (EC 50 <150 nM) was correlated to a ratio > 0.4. This result is in agreement with the high affinity of ABT-737 for Bcl-2 in contrast to Mcl-1. Induction of apoptosis may be due to the displacement of Bim, Puma or Bik from their endogenous complexes with Bcl-2, as demonstrated by immunoprecipitation assays. Interestingly, we demonstrated that all sensitive HMCLs harbored a t(11;14) while 77% (7 out of 9) of t(11;14) HMCLs are sensitive to ABT-737. Then, interrogation of the public expression database of MM patients showed that the Bcl-2/Mcl-1 ratio of both t(11;14) (median 0.29, range 0.05–0.71) and hyperdiploid (median 0.24, range 0.04–0.79) patients was significantly higher to all other groups of patients (p<.001). In order to fairly identify MM patients expressing high Bcl-2/Mcl-1 ratio we set up a flow cytometry assay. Preliminary results confirmed that primary myeloma cells with a high Bcl-2/Mcl-1 ratio are also highly sensitive to ABT-737. Altogether, the very high sensitivity of Bcl-2 high Mcl-1weak HMCLs and primary myeloma cells to ABT-737 (similar to the one of CLL) supports the idea of a clinical trial using Bcl-2 antagonists in a selected subset of t(11;14) and hyperdiploid Multiple Myeloma patients. Disclosures: Avet-Loiseau: Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees." @default.
• W2556353357 created "2016-11-30" @default.
• W2556353357 creator A5003041443 @default.
• W2556353357 creator A5016122215 @default.
• W2556353357 creator A5033010026 @default.
• W2556353357 creator A5051471778 @default.
• W2556353357 creator A5058940187 @default.
• W2556353357 creator A5063422967 @default.
• W2556353357 creator A5068580383 @default.
• W2556353357 creator A5069230123 @default.
• W2556353357 creator A5074449943 @default.
• W2556353357 date "2010-11-19" @default.
• W2556353357 modified "2023-10-11" @default.
• W2556353357 title "High Bcl-2/Mcl-1 Gene Expression Ratio Identifies Molecular Sub-Groups of Multiple Myeloma Patients Extremely Sensitive to ABT-737" @default.
• W2556353357 doi "https://doi.org/10.1182/blood.v116.21.4061.4061" @default.
• W2556353357 hasPublicationYear "2010" @default.
• W2556353357 type Work @default.
• W2556353357 sameAs 2556353357 @default.
• W2556353357 citedByCount "0" @default.
• W2556353357 crossrefType "journal-article" @default.
• W2556353357 hasAuthorship W2556353357A5003041443 @default.
• W2556353357 hasAuthorship W2556353357A5016122215 @default.
• W2556353357 hasAuthorship W2556353357A5033010026 @default.
• W2556353357 hasAuthorship W2556353357A5051471778 @default.
• W2556353357 hasAuthorship W2556353357A5058940187 @default.
• W2556353357 hasAuthorship W2556353357A5063422967 @default.
• W2556353357 hasAuthorship W2556353357A5068580383 @default.
• W2556353357 hasAuthorship W2556353357A5069230123 @default.
• W2556353357 hasAuthorship W2556353357A5074449943 @default.
• W2556353357 hasConcept C153911025 @default.
• W2556353357 hasConcept C173396325 @default.
• W2556353357 hasConcept C174510640 @default.
• W2556353357 hasConcept C190283241 @default.
• W2556353357 hasConcept C203014093 @default.
• W2556353357 hasConcept C2776364478 @default.
• W2556353357 hasConcept C2777478702 @default.
• W2556353357 hasConcept C31573885 @default.
• W2556353357 hasConcept C502942594 @default.
• W2556353357 hasConcept C53227056 @default.
• W2556353357 hasConcept C54355233 @default.
• W2556353357 hasConcept C71924100 @default.
• W2556353357 hasConcept C81885089 @default.
• W2556353357 hasConcept C86803240 @default.
• W2556353357 hasConceptScore W2556353357C153911025 @default.
• W2556353357 hasConceptScore W2556353357C173396325 @default.
• W2556353357 hasConceptScore W2556353357C174510640 @default.
• W2556353357 hasConceptScore W2556353357C190283241 @default.
• W2556353357 hasConceptScore W2556353357C203014093 @default.
• W2556353357 hasConceptScore W2556353357C2776364478 @default.
• W2556353357 hasConceptScore W2556353357C2777478702 @default.
• W2556353357 hasConceptScore W2556353357C31573885 @default.
• W2556353357 hasConceptScore W2556353357C502942594 @default.
• W2556353357 hasConceptScore W2556353357C53227056 @default.
• W2556353357 hasConceptScore W2556353357C54355233 @default.
• W2556353357 hasConceptScore W2556353357C71924100 @default.
• W2556353357 hasConceptScore W2556353357C81885089 @default.
• W2556353357 hasConceptScore W2556353357C86803240 @default.
• W2556353357 hasLocation W25563533571 @default.
• W2556353357 hasOpenAccess W2556353357 @default.
• W2556353357 hasPrimaryLocation W25563533571 @default.
• W2556353357 hasRelatedWork W1123756285 @default.
• W2556353357 hasRelatedWork W2031975865 @default.
• W2556353357 hasRelatedWork W2061425058 @default.
• W2556353357 hasRelatedWork W2118863989 @default.
• W2556353357 hasRelatedWork W2291176625 @default.
• W2556353357 hasRelatedWork W2332768240 @default.
• W2556353357 hasRelatedWork W2339591638 @default.
• W2556353357 hasRelatedWork W2417191938 @default.
• W2556353357 hasRelatedWork W2463716169 @default.
• W2556353357 hasRelatedWork W2556683185 @default.
• W2556353357 hasRelatedWork W2558122676 @default.
• W2556353357 hasRelatedWork W2567669180 @default.
• W2556353357 hasRelatedWork W2576782710 @default.
• W2556353357 hasRelatedWork W2577884059 @default.
• W2556353357 hasRelatedWork W2585746906 @default.
• W2556353357 hasRelatedWork W2586567488 @default.
• W2556353357 hasRelatedWork W2587869172 @default.
• W2556353357 hasRelatedWork W2921598710 @default.
• W2556353357 hasRelatedWork W65177702 @default.
• W2556353357 hasRelatedWork W68676002 @default.
• W2556353357 isParatext "false" @default.
• W2556353357 isRetracted "false" @default.
• W2556353357 magId "2556353357" @default.
• W2556353357 workType "article" @default.