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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Protection of CLL B cells by a follicular dendritic cell line is dependent on induction of Mcl-1.
Irene M. Pedersen,Shinichi Kitada,Lorenzo M. Leoni,Juan M. Zapata,James G. Karras,Nobuhiro Tsukada,Thomas J. Kipps,Yong Sung Choi,Frank C. Bennett,John C. Reed +9 more
TL;DR: HK cells protect CLL B cells against apoptosis, at least in part through a CD44-dependent mechanism involving up-regulation of Mcl-1, and this mechanism is distinct from that achieved by CD40 ligation.
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Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma.
Annuska M. Glas,Laurent Knoops,Leonie J. M. J. Delahaye,Marie José Kersten,Robby E. Kibbelaar,L. F. A. Wessels,Ryan van Laar,J. Han van Krieken,Joke W. Baars,John M. M. Raemaekers,Philip M. Kluin,Laura J. van't Veer,Daphne de Jong +12 more
TL;DR: The identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior is supported.
Journal ArticleDOI
Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia
Valter Gattei,Pietro Bulian,Maria Ilaria Del Principe,Antonella Zucchetto,Luca Maurillo,Francesco Buccisano,Riccardo Bomben,Michele Dal-Bo,Fabrizio Luciano,Francesca Rossi,Massimo Degan,Sergio Amadori,Giovanni Del Poeta +12 more
TL;DR: Findings support the introduction of CD49d detection in routine prognostic assessment of CLL patients, and suggest both pathogenetic and therapeutic implications for CD 49d expression in CLL.
Journal ArticleDOI
Number of CD4+ Cells and Location of Forkhead Box Protein P3–Positive Cells in Diagnostic Follicular Lymphoma Tissue Microarrays Correlates With Outcome
Abigail M. Lee,Andrew Clear,Maria Calaminici,Andrew Davies,Suzanne Jordan,Finlay MacDougall,Janet Matthews,Andrew Norton,John G. Gribben,T. Andrew Lister,Lindsey K. Goff +10 more
TL;DR: Differences in immune cell composition of the diagnostic FL lymph node immune microenvironment have the potential for use as prognostic biomarkers in a routine histopathology setting.
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Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B cell chronic lymphocytic leukemia
Andrea Bürkle,Matthias Niedermeier,Annette Schmitt-Gräff,William G. Wierda,Michael J. Keating,Jan A. Burger +5 more
TL;DR: CXCR5 plays a role in CLL cell positioning and cognate interactions between CLL and CXCL13-secreting CD68+ accessory cells in lymphoid tissues, and levels correlated with beta2 microglobulin are reported.
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