FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3029798082> ?p ?o ?g. }

• W3029798082 abstract "Abstract IKAROS family zinc finger 1 ( IKZF1 ) alterations represent a diverse group of genetic lesions that are associated with an increased risk of relapse in B-lymphoblastic leukemia (B-ALL). Due to the heterogeneity of concomitant lesions it remains unclear how IKZF1 abnormalities directly affect cell function and therapy resistance and whether their consideration as a prognostic indicator is valuable in improving outcome. We used CRISPR/Cas9 to engineer multiple panels of isogeneic lymphoid leukemia cell lines with a spectrum of IKZF1 lesions in order to measure changes in chemosensitivity, gene expression, cell cycle, and in vivo engraftment dynamics that can be directly linked to loss of IKAROS protein. IKZF1 knockout and heterozygous null cells displayed relative resistance to a number of commonly employed therapies for B-ALL including dexamethasone, vincristine, asparaginase, and daunorubicin. Transcription profiling revealed a stem/myeloid cell-like phenotype and JAK/STAT upregulation after IKAROS loss. We also used a CRISPR homology-directed repair (HDR) strategy to knock-in the dominant-negative IK6 isoform tagged with GFP into the endogenous locus and observed a similar drug resistance profile with the exception of retained sensitivity to dexamethasone. Interestingly, IKZF1 knockout and IK6 knock-in cells both have significantly increased sensitivity to cytarabine, suggesting intensification of nucleoside analog therapy may be specifically effective for IKZF1 -deleted B-ALL. Both types of IKZF1 lesions decreased survival time of xenograft mice, with higher numbers of circulating blasts and increased organ infiltration. Given these findings, exact specification of IKZF1 status in patients may be a beneficial addition to risk stratification and could inform therapy. Key points Engineered IKZF1 perturbations result in a stem-cell like expression signature, enhanced engraftment in vivo, and multi-drug resistance Loss of IKAROS may result in new vulnerabilities due to increased sensitivity to cytarabine and upregulation of JAK/STAT and mAb targets" @default.
• W3029798082 created "2020-06-05" @default.
• W3029798082 creator A5002811461 @default.
• W3029798082 creator A5003796424 @default.
• W3029798082 creator A5031330541 @default.
• W3029798082 creator A5031457493 @default.
• W3029798082 creator A5035483511 @default.
• W3029798082 creator A5036550103 @default.
• W3029798082 creator A5061427391 @default.
• W3029798082 creator A5069948911 @default.
• W3029798082 creator A5074463940 @default.
• W3029798082 creator A5076644963 @default.
• W3029798082 creator A5080886590 @default.
• W3029798082 creator A5083993271 @default.
• W3029798082 creator A5084353341 @default.
• W3029798082 date "2020-05-27" @default.
• W3029798082 modified "2023-09-27" @default.
• W3029798082 title "Modeling IKZF1 lesions in B-ALL reveals distinct chemosensitivity patterns and potential therapeutic vulnerabilities" @default.
• W3029798082 cites W1499446950 @default.
• W3029798082 cites W1573078268 @default.
• W3029798082 cites W1901988103 @default.
• W3029798082 cites W1915704240 @default.
• W3029798082 cites W1973054937 @default.
• W3029798082 cites W1975249675 @default.
• W3029798082 cites W1976489234 @default.
• W3029798082 cites W1984065010 @default.
• W3029798082 cites W1989645452 @default.
• W3029798082 cites W2015345028 @default.
• W3029798082 cites W2019338546 @default.
• W3029798082 cites W2023695790 @default.
• W3029798082 cites W2027018998 @default.
• W3029798082 cites W2035749206 @default.
• W3029798082 cites W2037305083 @default.
• W3029798082 cites W2039293047 @default.
• W3029798082 cites W2040329520 @default.
• W3029798082 cites W2048365283 @default.
• W3029798082 cites W2055282601 @default.
• W3029798082 cites W2056166587 @default.
• W3029798082 cites W2063530002 @default.
• W3029798082 cites W2064667001 @default.
• W3029798082 cites W2068412287 @default.
• W3029798082 cites W2082973537 @default.
• W3029798082 cites W2106070783 @default.
• W3029798082 cites W2106960031 @default.
• W3029798082 cites W2134118606 @default.
• W3029798082 cites W2153588260 @default.
• W3029798082 cites W2163001955 @default.
• W3029798082 cites W2166089525 @default.
• W3029798082 cites W2210631642 @default.
• W3029798082 cites W2321772913 @default.
• W3029798082 cites W2535622376 @default.
• W3029798082 cites W2587039580 @default.
• W3029798082 cites W2619312802 @default.
• W3029798082 cites W2736638928 @default.
• W3029798082 cites W2740576382 @default.
• W3029798082 cites W2794056739 @default.
• W3029798082 cites W2801416175 @default.
• W3029798082 cites W2883981088 @default.
• W3029798082 cites W2890477656 @default.
• W3029798082 cites W2996578960 @default.
• W3029798082 cites W779901821 @default.
• W3029798082 cites W81453212 @default.
• W3029798082 doi "https://doi.org/10.1101/2020.05.26.109579" @default.
• W3029798082 hasPublicationYear "2020" @default.
• W3029798082 type Work @default.
• W3029798082 sameAs 3029798082 @default.
• W3029798082 citedByCount "0" @default.
• W3029798082 crossrefType "posted-content" @default.
• W3029798082 hasAuthorship W3029798082A5002811461 @default.
• W3029798082 hasAuthorship W3029798082A5003796424 @default.
• W3029798082 hasAuthorship W3029798082A5031330541 @default.
• W3029798082 hasAuthorship W3029798082A5031457493 @default.
• W3029798082 hasAuthorship W3029798082A5035483511 @default.
• W3029798082 hasAuthorship W3029798082A5036550103 @default.
• W3029798082 hasAuthorship W3029798082A5061427391 @default.
• W3029798082 hasAuthorship W3029798082A5069948911 @default.
• W3029798082 hasAuthorship W3029798082A5074463940 @default.
• W3029798082 hasAuthorship W3029798082A5076644963 @default.
• W3029798082 hasAuthorship W3029798082A5080886590 @default.
• W3029798082 hasAuthorship W3029798082A5083993271 @default.
• W3029798082 hasAuthorship W3029798082A5084353341 @default.
• W3029798082 hasBestOaLocation W30297980821 @default.
• W3029798082 hasConcept C203014093 @default.
• W3029798082 hasConcept C2776694085 @default.
• W3029798082 hasConcept C2776755627 @default.
• W3029798082 hasConcept C2778041864 @default.
• W3029798082 hasConcept C2778461978 @default.
• W3029798082 hasConcept C2778729363 @default.
• W3029798082 hasConcept C2779429289 @default.
• W3029798082 hasConcept C2781021840 @default.
• W3029798082 hasConcept C502942594 @default.
• W3029798082 hasConcept C54355233 @default.
• W3029798082 hasConcept C86803240 @default.
• W3029798082 hasConceptScore W3029798082C203014093 @default.
• W3029798082 hasConceptScore W3029798082C2776694085 @default.
• W3029798082 hasConceptScore W3029798082C2776755627 @default.
• W3029798082 hasConceptScore W3029798082C2778041864 @default.
• W3029798082 hasConceptScore W3029798082C2778461978 @default.
• W3029798082 hasConceptScore W3029798082C2778729363 @default.
• W3029798082 hasConceptScore W3029798082C2779429289 @default.

• next