The microenvironment in mature B-cell malignancies: a target for new treatment strategies
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TLDR
A paradigm shift in the treatment of selected B-cell malignancies is anticipated, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role.About:
This article is published in Blood.The article was published on 2009-10-15 and is currently open access. It has received 543 citations till now.read more
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The lymph node microenvironment promotes B-cell receptor signaling, NF-κB activation, and tumor proliferation in chronic lymphocytic leukemia
Yair Herishanu,Patricia Pérez-Galán,Delong Liu,Angelique Biancotto,Stefania Pittaluga,Berengere Vire,Federica Gibellini,Ndegwa Njuguna,Elinor Lee,Lawrence S. Stennett,Nalini Raghavachari,Poching Liu,J. Philip McCoy,Mark Raffeld,Maryalice Stetler-Stevenson,Constance M. Yuan,Richard M. Sherry,Diane C. Arthur,Irina Maric,Therese White,Gerald E. Marti,Peter J. Munson,Wyndham H. Wilson,Adrian Wiestner +23 more
TL;DR: The disruption of tumor microenvironment interactions and the inhibition of BCR signaling as promising therapeutic strategies in CLL are identified.
Journal ArticleDOI
Antibody-modified T cells: CARs take the front seat for hematologic malignancies
TL;DR: The results of the reported clinical trials are reviewed and the progress and key emerging factors that may play a role in effecting tumor responses are discussed, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies.
Journal ArticleDOI
The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo
Sabine Ponader,Shih Shih Chen,Joseph J. Buggy,Kumudha Balakrishnan,Varsha Gandhi,William G. Wierda,Michael J. Keating,Susan O'Brien,Nicholas Chiorazzi,Jan A. Burger +9 more
TL;DR: It is demonstrated that PCI-32765 effectively inhibits CLL cell migration and survival, possibly explaining some of the characteristic clinical activity of this new targeted agent.
Journal ArticleDOI
The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia
Julia Hoellenriegel,Sarah A. Meadows,Mariela Sivina,William G. Wierda,Hagop M. Kantarjian,Michael J. Keating,Neill A. Giese,Susan O'Brien,Albert S. Yu,Langdon L. Miller,Brian J. Lannutti,Jan A. Burger +11 more
TL;DR: CAL-101 displays a dual mechanism of action, directly decreasing cell survival while reducing interactions that retain CLL cells in protective tissue microenvironments, and a roadmap for future therapeutic development.
Journal ArticleDOI
The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia
Martin F. M. de Rooij,Annemieke Kuil,Christian R. Geest,Eric Eldering,Betty Y. Chang,Joseph J. Buggy,Steven T. Pals,Marcel Spaargaren +7 more
TL;DR: The data indicate that inhibition of BTK by PCI-32765 overcomes BCR- and chemokine-controlled integrin-mediated retention and homing of malignant B cells in their growth- and survival-supporting lymph node and bone marrow microenvironment, which results in clinically evident CLL regression.
References
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TL;DR: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.
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B lymphocytes: how they develop and function
TL;DR: P perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B- cell development and selection.
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