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Targeting Bruton's Tyrosine Kinase in CLL.
Ahn IE, Brown JR. Ahn IE, et al. Front Immunol. 2021 Jun 23;12:687458. doi: 10.3389/fimmu.2021.687458. eCollection 2021. Front Immunol. 2021. PMID: 34248972 Free PMC article. Review.
Disease progression on covalent BTKis, driven by histologic transformation or selective expansion of BTK and PLCG2 mutated CLL clones, remains a major challenge in the field. Fixed duration combination regimens and reversible BTKis with non-covalent binding chemistry hold …
Disease progression on covalent BTKis, driven by histologic transformation or selective expansion of BTK and PLCG2 mutated CLL clones …
Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors.
Wang E, Mi X, Thompson MC, Montoya S, Notti RQ, Afaghani J, Durham BH, Penson A, Witkowski MT, Lu SX, Bourcier J, Hogg SJ, Erickson C, Cui D, Cho H, Singer M, Totiger TM, Chaudhry S, Geyer M, Alencar A, Linley AJ, Palomba ML, Coombs CC, Park JH, Zelenetz A, Roeker L, Rosendahl M, Tsai DE, Ebata K, Brandhuber B, Hyman DM, Aifantis I, Mato A, Taylor J, Abdel-Wahab O. Wang E, et al. N Engl J Med. 2022 Feb 24;386(8):735-743. doi: 10.1056/NEJMoa2114110. N Engl J Med. 2022. PMID: 35196427 Free PMC article.
We found mutations (V416L, A428D, M437R, T474I, and L528W) that were clustered in the kinase domain of BTK and that conferred resistance to both noncovalent BTK inhibitors and certain covalent BTK inhibitors. Mutations in BTK or phospholipase C gamma 2 …
We found mutations (V416L, A428D, M437R, T474I, and L528W) that were clustered in the kinase domain of BTK and that conferred resistance to …
PLCG2-associated immune dysregulation (PLAID) comprises broad and distinct clinical presentations related to functional classes of genetic variants.
Baysac K, Sun G, Nakano H, Schmitz EG, Cruz AC, Fisher C, Bailey AC; PLCG2-Immune Dysregulation Working Group; Mace E, Milner JD, Ombrello MJ. Baysac K, et al. J Allergy Clin Immunol. 2024 Jan;153(1):230-242. doi: 10.1016/j.jaci.2023.08.036. Epub 2023 Sep 26. J Allergy Clin Immunol. 2024. PMID: 37769878 Free PMC article.
BACKGROUND: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dominant immune dysregulation (ID), PLCgamma2-associated antibody deficiency and immune dysregulation (PLAID) and autoinflammatory PLAID (APLAI …
BACKGROUND: Pathogenic variants of phospholipase C gamma 2 (PLCG2) cause 2 related forms of autosomal-dom …
Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.
de Rojas I, Moreno-Grau S, Tesi N, Grenier-Boley B, Andrade V, Jansen IE, Pedersen NL, Stringa N, Zettergren A, Hernández I, Montrreal L, Antúnez C, Antonell A, Tankard RM, Bis JC, Sims R, Bellenguez C, Quintela I, González-Perez A, Calero M, Franco-Macías E, Macías J, Blesa R, Cervera-Carles L, Menéndez-González M, Frank-García A, Royo JL, Moreno F, Huerto Vilas R, Baquero M, Diez-Fairen M, Lage C, García-Madrona S, García-González P, Alarcón-Martín E, Valero S, Sotolongo-Grau O, Ullgren A, Naj AC, Lemstra AW, Benaque A, Pérez-Cordón A, Benussi A, Rábano A, Padovani A, Squassina A, de Mendonça A, Arias Pastor A, Kok AAL, Meggy A, Pastor AB, Espinosa A, Corma-Gómez A, Martín Montes A, Sanabria Á, DeStefano AL, Schneider A, Haapasalo A, Kinhult Ståhlbom A, Tybjærg-Hansen A, Hartmann AM, Spottke A, Corbatón-Anchuelo A, Rongve A, Borroni B, Arosio B, Nacmias B, Nordestgaard BG, Kunkle BW, Charbonnier C, Abdelnour C, Masullo C, Martínez Rodríguez C, Muñoz-Fernandez C, Dufouil C, Graff C, Ferreira CB, Chillotti C, Reynolds CA, Fenoglio C, Van Broeckhoven C, Clark C, Pisanu C, Satizabal CL, Holmes C, Buiza-Rueda D, Aarsland D, Rujescu D, Alcolea D, Galimberti D, Wallon D, Seripa D, Grün… See abstract for full author list ➔ de Rojas I, et al. Nat Commun. 2021 Jun 7;12(1):3417. doi: 10.1038/s41467-021-22491-8. Nat Commun. 2021. PMID: 34099642 Free PMC article.
Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset …
Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in …
A Review of Resistance Mechanisms to Bruton's Kinase Inhibitors in Chronic Lymphocytic Leukemia.
Wiśniewski K, Puła B. Wiśniewski K, et al. Int J Mol Sci. 2024 May 11;25(10):5246. doi: 10.3390/ijms25105246. Int J Mol Sci. 2024. PMID: 38791284 Free PMC article. Review.
In recent years, it has been demonstrated that the predominant mechanisms of resistance to BTKi are mutations in BTK or phospholipase Cgamma2 (PLCG2). Some differences in the mechanisms of resistance to covalent BTKi have been identified despite their similar mechanism of …
In recent years, it has been demonstrated that the predominant mechanisms of resistance to BTKi are mutations in BTK or phospholipase Cgamma …
Identification of Molecular Subtypes and a Prognostic Signature Based on Inflammation-Related Genes in Colon Adenocarcinoma.
Qiu C, Shi W, Wu H, Zou S, Li J, Wang D, Liu G, Song Z, Xu X, Hu J, Geng H. Qiu C, et al. Front Immunol. 2021 Dec 23;12:769685. doi: 10.3389/fimmu.2021.769685. eCollection 2021. Front Immunol. 2021. PMID: 35003085 Free PMC article.
A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic factor. ...
A prognostic signature including four genes (PLCG2, TIMP1, BDNF and IL13) was also constructed and was an independent prognostic fact …
Cognitively healthy centenarians are genetically protected against Alzheimer's disease.
Tesi N, van der Lee S, Hulsman M, van Schoor NM, Huisman M, Pijnenburg Y, van der Flier WM, Reinders M, Holstege H. Tesi N, et al. Alzheimers Dement. 2024 Jun;20(6):3864-3875. doi: 10.1002/alz.13810. Epub 2024 Apr 18. Alzheimers Dement. 2024. PMID: 38634500 Free PMC article.
The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 10(-71)), and 2-fold lower compared to age-matched controls (P = 5.83 1 …
The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to …
Mutational profile in previously treated patients with chronic lymphocytic leukemia progression on acalabrutinib or ibrutinib.
Woyach JA, Jones D, Jurczak W, Robak T, Illés Á, Kater AP, Ghia P, Byrd JC, Seymour JF, Long S, Mohamed N, Benrashid S, Lai TH, De Jesus G, Lai R, de Bruin G, Rule S, Munugalavadla V. Woyach JA, et al. Blood. 2024 Sep 5;144(10):1061-1068. doi: 10.1182/blood.2023023659. Blood. 2024. PMID: 38754046 Free PMC article. Clinical Trial.
Six acalabrutinib-treated patients and 1 ibrutinib-treated patient had emergent TP53/BTK comutations. Emergent PLCG2 mutations occurred in 3 acalabrutinib-treated (6%) and 6 ibrutinib-treated patients (20%). One acalabrutinib-treated patient and 4 ibrutinib-treated patient …
Six acalabrutinib-treated patients and 1 ibrutinib-treated patient had emergent TP53/BTK comutations. Emergent PLCG2 mutations occurr …
PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer.
Liu C, Li J, Xu F, Chen L, Ni M, Wu J, Zhao H, Wu Y, Li J, Wu X, Chen X. Liu C, et al. Mol Cancer. 2024 May 22;23(1):111. doi: 10.1186/s12943-024-02025-8. Mol Cancer. 2024. PMID: 38778348 Free PMC article.
Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. ...CONCLUSIONS: Our results demonstrate that D …
Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This …
PLCG2 can exist in eccDNA and contribute to the metastasis of non-small cell lung cancer by regulating mitochondrial respiration.
Yang Y, Yang Y, Huang H, Song T, Mao S, Liu D, Zhang L, Li W. Yang Y, et al. Cell Death Dis. 2023 Apr 8;14(4):257. doi: 10.1038/s41419-023-05755-7. Cell Death Dis. 2023. PMID: 37031207 Free PMC article.
The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT-PCR and western blotting experiments were used to verify the expression level of PLCG2. ...We also demonstrated that PLCG2 can promote me …
The upregulated candidate eccDNA-encoding PLCG2 was validated by routine PCR. Plasmid transfection, RNA interference, qRT-PCR and wes …
92 results