Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2009-3-27
pubmed:abstractText
In lymphatic tissues, chronic lymphocytic leukemia (CLL) cells are interspersed with CD68(+) nurselike cells (NLCs), T cells, and other stromal cells that constitute the leukemia microenvironment. However, the mechanism regulating colocalization of CLL and these accessory cells are largely unknown. To dissect the molecular cross talk between CLL and NLCs, we profiled the gene expression of CD19-purified CLL cells before and after coculture with NLCs. NLC coculture induced high-level expression of B-cell maturation antigen and 2 chemoattractants (CCL3, CCL4) by CLL cells. CCL3/CCL4 induction in NLC cocultures correlated with ZAP-70 expression by CLL cells. High CCL3/CCL4 protein levels were found in CLL cocultures with NLCs, and CCL3/CCL4 induction was abrogated by R406, a Syk inhibitor, suggesting that NLCs induce these chemokines via B-cell receptor (BCR) activation. BCR triggering also caused robust CCL3/CCL4 protein secretion by CLL cells. High CCL3 and CCL4 plasma levels in CLL patients suggest that this pathway plays a role in vivo. These studies reveal a novel mechanism of cross talk between CLL cells and their microenvironment, namely, the secretion of 2 T-cell chemokines in response to NLC coculture and BCR stimulation. Through these chemokines, CLL cells can recruit accessory cells and thereby actively create a supportive microenvironment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
113
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3050-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19074730-Antibodies, Anti-Idiotypic, pubmed-meshheading:19074730-B-Lymphocytes, pubmed-meshheading:19074730-Chemokine CCL3, pubmed-meshheading:19074730-Chemokine CCL4, pubmed-meshheading:19074730-Coculture Techniques, pubmed-meshheading:19074730-Culture Media, Conditioned, pubmed-meshheading:19074730-Gene Expression Profiling, pubmed-meshheading:19074730-Gene Expression Regulation, Leukemic, pubmed-meshheading:19074730-Humans, pubmed-meshheading:19074730-Leukemia, Myeloid, pubmed-meshheading:19074730-Lymphocyte Activation, pubmed-meshheading:19074730-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:19074730-Proto-Oncogene Proteins c-bcr, pubmed-meshheading:19074730-T-Lymphocytes, pubmed-meshheading:19074730-Tumor Cells, Cultured, pubmed-meshheading:19074730-Up-Regulation, pubmed-meshheading:19074730-ZAP-70 Protein-Tyrosine Kinase
pubmed:year
2009
pubmed:articleTitle
High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation.
pubmed:affiliation
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA. jaburger@mdanderson.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't