B cell receptor signaling in chronic lymphocytic leukemia.
Jan A. Burger,Nicholas Chiorazzi +1 more
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TLDR
The evolution of this field is discussed, from BCR-related prognostic markers, to mechanisms of BCR activation, and targeting of B CR-associated kinases, the emerging Achilles' heel in CLL pathogenesis.About:
This article is published in Trends in Immunology.The article was published on 2013-12-01 and is currently open access. It has received 378 citations till now. The article focuses on the topics: B-cell receptor & Chronic lymphocytic leukemia.read more
Citations
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Journal ArticleDOI
Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment
TL;DR: A large number of patients diagnosed with chronic lymphocytic leukemia have a history of atypical clinical course, suggesting that the disease typically occurs in elderly patients and has a highly variable clinical course.
Journal ArticleDOI
Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment.
TL;DR: Chronic lymphocytic leukemia is the commonest leukemia in western countries and typically occurs in elderly patients and has a highly variable clinical course.
Journal ArticleDOI
Targeting B cell receptor signalling in cancer: preclinical and clinical advances
Jan A. Burger,Adrian Wiestner +1 more
TL;DR: B cells and B CR-related kinases also play a role in the microenvironment of solid tumours, such as squamous cell carcinoma and pancreatic cancer, and therefore targeting B cells or BCR- related kinases may have anticancer activity beyond B cell malignancies.
Journal ArticleDOI
The molecular pathogenesis of chronic lymphocytic leukaemia
TL;DR: This Review focuses on recent insights into the understanding of CLL biology, with emphasis on the role of genetic lesions in the initiation and clinical progression of Cll.
Journal ArticleDOI
Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition
Jan A. Burger,Dan A. Landau,Amaro Taylor-Weiner,Ivana Bozic,Huidan Zhang,Huidan Zhang,Huidan Zhang,Kristopher A. Sarosiek,Lili Wang,Chip Stewart,Jean Fan,Julia Hoellenriegel,Mariela Sivina,Adrian M. Dubuc,Cameron Fraser,Yu Long Han,Shuqiang Li,Kenneth J. Livak,Lihua Zou,Youzhong Wan,Sergej Konoplev,Carrie Sougnez,Jennifer R. Brown,Lynne V. Abruzzo,Scott L. Carter,Michael J. Keating,Matthew S. Davids,William G. Wierda,Kristian Cibulskis,Thorsten Zenz,Lillian Werner,Paola Dal Cin,Peter Kharchencko,Donna Neuberg,Hagop M. Kantarjian,Eric S. Lander,Stacey Gabriel,Susan O'Brien,Anthony Letai,David A. Weitz,Martin A. Nowak,Gad Getz,Catherine J. Wu,Catherine J. Wu,Catherine J. Wu +44 more
TL;DR: It is demonstrated that the ibrutinib therapy favours selection and expansion of rare subclones already present before ibrUTinib treatment, and insight is provided into the heterogeneity of genetic changes associated with ibrutsinib resistance.
References
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Journal ArticleDOI
Impaired B and T Cell Antigen Receptor Signaling in p110δ PI 3-Kinase Mutant Mice
Klaus Okkenhaug,Antonio Bilancio,Géraldine Farjot,Helen Priddle,Sara Sancho,Emma Peskett,Wayne Pearce,Stephen Meek,Ashreena Salpekar,Michael D. Waterfield,Michael D. Waterfield,Andrew J.H. Smith,Bart Vanhaesebroeck,Bart Vanhaesebroeck +13 more
TL;DR: Results reveal a selective role for p110δ in immunity and suggest second messenger signals downstream of tyrosine kinases influence cell metabolism, growth, proliferation, differentiation, motility, and survival.
Journal ArticleDOI
ZAP-70 Compared with Immunoglobulin Heavy-Chain Gene Mutation Status as a Predictor of Disease Progression in Chronic Lymphocytic Leukemia
Laura Z. Rassenti,Lang Huynh,Tracy L. Toy,Liguang Chen,Michael J. Keating,John G. Gribben,Donna Neuberg,Ian W. Flinn,Kanti R. Rai,John C. Byrd,Neil E. Kay,Andrew W. Greaves,Arthur Weiss,Thomas J. Kipps +13 more
TL;DR: Although the presence of an unmutated IgV(H) gene is strongly associated with the expression of Zap-70, ZAP-70 is a stronger predictor of the need for treatment in B-cell CLL.
Journal ArticleDOI
Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors.
Franco Fais,Fabio Ghiotto,Shiori Hashimoto,Brian Sellars,Angelo Valetto,Steven L. Allen,Philip Schulman,Vincent Vinciguerra,Kanti R. Rai,Laura Z. Rassenti,Thomas J. Kipps,Guillaume Dighiero,Harry W. Schroeder,Manlio Ferrarini,Nicholas Chiorazzi +14 more
TL;DR: These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.
Journal ArticleDOI
BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control.
TL;DR: Inhibition of BCL-6 function initiated changes indicative of plasmacytic differentiation, including decreased expression of c-Myc and increased expression of the cell cycle inhibitor p27kip1, which suggest that malignant transformation by B CL-6 involves inhibition of differentiation and enhanced proliferation.
Journal ArticleDOI
Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice
David J. Rawlings,Douglas C. Saffran,Satoshi Tsukada,David A. Largaespada,J. Christopher Grimaldi,Lucie Cohen,Randolph N. Mohr,J. Fernando Bazan,Maureen C. Howard,Neal G. Copeland,Nancy A. Jenkins,Owen N. Witte +11 more
TL;DR: The Btk gene, btk, was mapped to the xid region of the mouse X chromosome by interspecific backcross analysis and a single conserved residue within the amino terminal unique region of Btk was mutated in XID mice, probably interferes with normal B cell signaling mediated by Btk protein interactions.
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