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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Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765.
Sarah E. M. Herman,Amber Gordon,Erin Hertlein,Asha Ramanunni,Xiaoli Zhang,Samantha Jaglowski,Joseph M. Flynn,Jeffrey A. Jones,Kristie A. Blum,Joseph J. Buggy,Ahmed Hamdy,Amy J. Johnson,John C. Byrd +12 more
TL;DR: It is demonstrated that BTK protein and mRNA are significantly over expressed in CLL compared with normal B cells, and future efforts targeting BTK with the irreversible inhibitor PCI-32765 in clinical trials of CLL patients is warranted.
Journal ArticleDOI
Perinatal lethality and blocked b-cell development in mice lacking the tyrosine kinase syk
Martin R Turner,P. J. Mee,P. S. Costello,Owen Williams,A. A. Price,L. P. Duddy,M. T. Furlong,Robert L. Geahlen,Victor L. J. Tybulewicz +8 more
TL;DR: It is shown that Syk is not required for signalling through the IL-2 and G-CSF receptors, and a possible role for this protein in the production or maintenance of mature B cells is suggested.
Journal ArticleDOI
CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability
Brian J. Lannutti,Sarah A. Meadows,Sarah E. M. Herman,Adam Kashishian,Bart Steiner,Amy J. Johnson,John C. Byrd,Jeffrey W. Tyner,Marc M. Loriaux,Mike Deininger,Brian J. Druker,Kamal D. Puri,Roger G. Ulrich,Neill A. Giese +13 more
TL;DR: Using tumor cell lines and primary patient samples representing multiple B-cell malignancies, it is demonstrated that constitutive phosphatidylinositol-3-kinase pathway activation is p110δ-dependent, providing a rationale for the ongoing clinical evaluation of CAL-101.
Journal ArticleDOI
Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1.
Jan A. Burger,Nobuhiro Tsukada,Meike Burger,Nathan J. Zvaifler,Marie Dell'Aquila,Thomas J. Kipps +5 more
TL;DR: It is concluded that the blood of patients with CLL contains cells that can differentiate into adherent nurse-like cells that protect leukemia cells from undergoing spontaneous apoptosis through an SDF-1–dependent mechanism.
Journal ArticleDOI
Cellular and genetic mechanisms of self tolerance and autoimmunity
TL;DR: The mammalian immune system has an extraordinary potential for making receptors that sense and neutralize any chemical entity entering the body, and cellular mechanisms have evolved to control the activity of these ‘forbidden’ receptors and achieve immunological self tolerance.
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