Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 7-Day Trial for You or Your Team.

Learn More →

A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells

A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic... The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk−, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-κB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-κB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-κB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Leukemia Springer Journals

A sustained activation of PI3K/NF-κB pathway is critical for the survival of chronic lymphocytic leukemia B cells

Download PDF
10 pages

Loading next page...
 
/lp/springer-journals/a-sustained-activation-of-pi3k-nf-b-pathway-is-critical-for-the-0rNhoyR2vB

References (75)

Publisher
Springer Journals
Copyright
Copyright © 2004 by Nature Publishing Group
Subject
Medicine & Public Health; Medicine/Public Health, general; Internal Medicine; Intensive / Critical Care Medicine; Cancer Research; Oncology; Hematology
ISSN
0887-6924
eISSN
1476-5551
DOI
10.1038/sj.leu.2403398
Publisher site
See Article on Publisher Site

Abstract

The progressive rise of mature CD5+ B lymphocytes, despite the low proportion of proliferating cells, has led to the notion that B cell chronic lymphocytic leukemia (B-CLL) is primarily related to defective apoptosis. The microenvironment likely plays a prominent role because the malignant cells progressively accumulate in vivo, whereas they rapidly undergo spontaneous apoptosis when cultured in vitro. To assess microenvironment-mediated survival signals, B-CLL cells were cultured with a murine fibroblast cell line, Ltk−, with and without an agonistic antibody to CD40. Spontaneous apoptosis was associated with the loss of Akt and NF-κB activities. Interactions with fibroblasts sustained a basal level of Akt and NF-κB activities, which was dependent on phosphatidylinositol-3 kinase (PI3K). Constitutive activity of the PI3K pathway in B-CLL cells when cultured with fibroblasts prevented the downregulation of the prosurvival Bcl-2 family protein Bcl-xL and the caspase inhibitor proteins FLIPL and XIAP, and consequently caspase-3 activation and apoptosis. CD40 crosslinking in B-CLL cells did not further prevent murine fibroblasts-mediated apoptosis but induced cell proliferation, which was associated with an increase of Akt and NF-κB activation compared with cells cultured with fibroblasts alone. The PI3K pathway seems to play a pivotal role in B-CLL cell survival and growth.

Journal

Leukemia – Springer Journals

Published: Jun 3, 2004

There are no references for this article.