FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380078716> ?p ?o ?g. }

• W4380078716 endingPage "661" @default.
• W4380078716 startingPage "658" @default.
• W4380078716 abstract "Introduction: Acquired BTK/PLCG2 mutations remain to be the driver of drug resistance. The underlying mechanisms need to be further explored. In this study, we retrospectively analyzed the clinical and biological characteristics of fifty-five BTKi-resistant CLL patients in our center and mapped the mutational landscape. Method: Fifty-five CLL patients who relapsed on BTKis were included and analyzed. 31 patients had matched sequencing data. High sensitivity droplet digital PCR (ddPCR) was additionally used for the detecting certain BTKC481S mutation. Result: The median age at the time of progression on BTKis was 57 years (Table 1). 86.3% (44/51) pts were IGHV unmutated. The most commonly used fragments were 1–69 (n = 10), 4–39 (n = 9), 3–9 (n = 6), and 3–48 (n = 6) (Figure 1). Resistance to BTKi occurred at a median exposure of 27.6 m in our cohort, medium exposure were 11.23 and 30.59 m for Richter transformation and CLL progression, respectively, p < 0.001). At progression time, 46.9% (23/49) had TP53 mutation, 24.5% (12/49) had ATM mutation, 22.4% (11/49) had EGR2 mutation, 22.4% (11/49) had SF3B1 mutation, 16.3% (8/49) had NOTCH1 mutation, and 10.2% (5/49) had KMT2D mutation. Mutational landscape is shown (Figure 2). No significant shift of mutation landscape was shown between these two timepoints. By integrating NGS and ddPCR results, BTK/PLCG2 mutation was detected in 49.0% (24/49) pts. ddPCR method may not available for the patients relapsed on the Ibrutinib, this may account for the low rate of acquired mutations detected in patients treated with Ibrutinib. Besides, spatial clonal heterogeneity affect the detection of acquired mutations. In 2 pts presented as LN enlargrment at progression, acquired mutations were not detected by NGS (bone marrow sample) while mutation was detected by ddPCR method or lymph node sample was used. The most common mutation was C481S (Figure 3), other mutations at the C481 site include C481R, C481Y, C481F. BTK T474 and L528 mutation were also found, concurrent with BTK 481 mutation or alone. 4 patients had PLCG2 mutations, including one concurrent with BTK mutation. TP53 mutations were analyzed among pts with paired gene mutation results. 16/31 pts were TP53 wildtype at both timepoints. No significant differences in TP53 mutation burden were shown (Figure 4). 4 pts gained TP53 mutation at disease progression, including one carried two different clones. 8/11 pts showed a reduction of existing clone (including 2 disappeared); 2 showed an expansion of existing clone; 1 carried a stable clone at low VAF (detected by ctDNA). Conclusion: IGHV unmutated status was dominant in our cohort and the most frequently used fragment were 1–69(n = 10), followed by 4–39(n = 9). Acquired BTK/PLCG2 mutations remained to be factors of BTKis resistance and the most common mutation was C481S in our cohort. No significant difference in TP53 mutation burden was found during the treatment of BTKis. The research was funded by: This study was supported by National Natural Science Foundation of China (Grant No. 82170166, No. 82100207, No. 82170186, No. 81970146, No. 81900167), Translational Research Grant of National Clinical Research Center for Hematology (2020ZKZB01), Six Talent Peaks Project in Jiangsu Province 2019 (Grant No. WSN-001) and Youth Talent support Project in Jiangsu Province Hospital (Grant No. YNRCQN035). Keywords: chronic lymphocytic leukemia (cll), molecular targeted therapies No conflicts of interests pertinent to the abstract." @default.
• W4380078716 created "2023-06-10" @default.
• W4380078716 creator A5000671830 @default.
• W4380078716 creator A5002911663 @default.
• W4380078716 creator A5005196775 @default.
• W4380078716 creator A5012712390 @default.
• W4380078716 creator A5014989673 @default.
• W4380078716 creator A5018556256 @default.
• W4380078716 creator A5029391631 @default.
• W4380078716 creator A5032767831 @default.
• W4380078716 creator A5037740266 @default.
• W4380078716 creator A5046175512 @default.
• W4380078716 creator A5090859164 @default.
• W4380078716 creator A5091196162 @default.
• W4380078716 date "2023-06-01" @default.
• W4380078716 modified "2023-09-23" @default.
• W4380078716 title "RESEARCH ON COHORT OF PATIENTS RELAPSED ON BRUTON TYROSINE KINASE INHIBITORS (BTKI)" @default.
• W4380078716 doi "https://doi.org/10.1002/hon.3165_510" @default.
• W4380078716 hasPublicationYear "2023" @default.
• W4380078716 type Work @default.
• W4380078716 citedByCount "0" @default.
• W4380078716 crossrefType "journal-article" @default.
• W4380078716 hasAuthorship W4380078716A5000671830 @default.
• W4380078716 hasAuthorship W4380078716A5002911663 @default.
• W4380078716 hasAuthorship W4380078716A5005196775 @default.
• W4380078716 hasAuthorship W4380078716A5012712390 @default.
• W4380078716 hasAuthorship W4380078716A5014989673 @default.
• W4380078716 hasAuthorship W4380078716A5018556256 @default.
• W4380078716 hasAuthorship W4380078716A5029391631 @default.
• W4380078716 hasAuthorship W4380078716A5032767831 @default.
• W4380078716 hasAuthorship W4380078716A5037740266 @default.
• W4380078716 hasAuthorship W4380078716A5046175512 @default.
• W4380078716 hasAuthorship W4380078716A5090859164 @default.
• W4380078716 hasAuthorship W4380078716A5091196162 @default.
• W4380078716 hasBestOaLocation W43800787161 @default.
• W4380078716 hasConcept C104317684 @default.
• W4380078716 hasConcept C126322002 @default.
• W4380078716 hasConcept C143998085 @default.
• W4380078716 hasConcept C2777609679 @default.
• W4380078716 hasConcept C2777938653 @default.
• W4380078716 hasConcept C2778461978 @default.
• W4380078716 hasConcept C48126324 @default.
• W4380078716 hasConcept C49105822 @default.
• W4380078716 hasConcept C501734568 @default.
• W4380078716 hasConcept C502942594 @default.
• W4380078716 hasConcept C54355233 @default.
• W4380078716 hasConcept C71924100 @default.
• W4380078716 hasConcept C72563966 @default.
• W4380078716 hasConcept C86803240 @default.
• W4380078716 hasConcept C90924648 @default.
• W4380078716 hasConceptScore W4380078716C104317684 @default.
• W4380078716 hasConceptScore W4380078716C126322002 @default.
• W4380078716 hasConceptScore W4380078716C143998085 @default.
• W4380078716 hasConceptScore W4380078716C2777609679 @default.
• W4380078716 hasConceptScore W4380078716C2777938653 @default.
• W4380078716 hasConceptScore W4380078716C2778461978 @default.
• W4380078716 hasConceptScore W4380078716C48126324 @default.
• W4380078716 hasConceptScore W4380078716C49105822 @default.
• W4380078716 hasConceptScore W4380078716C501734568 @default.
• W4380078716 hasConceptScore W4380078716C502942594 @default.
• W4380078716 hasConceptScore W4380078716C54355233 @default.
• W4380078716 hasConceptScore W4380078716C71924100 @default.
• W4380078716 hasConceptScore W4380078716C72563966 @default.
• W4380078716 hasConceptScore W4380078716C86803240 @default.
• W4380078716 hasConceptScore W4380078716C90924648 @default.
• W4380078716 hasIssue "S2" @default.
• W4380078716 hasLocation W43800787161 @default.
• W4380078716 hasOpenAccess W4380078716 @default.
• W4380078716 hasPrimaryLocation W43800787161 @default.
• W4380078716 hasRelatedWork W1967505760 @default.
• W4380078716 hasRelatedWork W1969483847 @default.
• W4380078716 hasRelatedWork W2315085516 @default.
• W4380078716 hasRelatedWork W2316407790 @default.
• W4380078716 hasRelatedWork W2330239290 @default.
• W4380078716 hasRelatedWork W2598717188 @default.
• W4380078716 hasRelatedWork W2603773853 @default.
• W4380078716 hasRelatedWork W2952239533 @default.
• W4380078716 hasRelatedWork W2964295425 @default.
• W4380078716 hasRelatedWork W2999832097 @default.
• W4380078716 hasVolume "41" @default.
• W4380078716 isParatext "false" @default.
• W4380078716 isRetracted "false" @default.
• W4380078716 workType "article" @default.