Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2010-11-5
pubmed:abstractText
The function of the intracellular protein hematopoietic cell-specific Lyn substrate-1 (HS1) in B lymphocytes is poorly defined. To investigate its role in migration, trafficking, and homing of leukemic B lymphocytes we have used B cells from HS1(-/-) mice, the HS1-silenced human chronic lymphocytic leukemia (CLL) MEC1 cell line and primary leukemic B cells from patients with CLL. We have used both in vitro and in vivo models and found that the lack of expression of HS1 causes several important functional effects. In vitro, we observed an impaired cytoskeletal remodeling that resulted in diminished cell migration, abnormal cell adhesion, and increased homotypic aggregation. In vivo, immunodeficient Rag2(-/-)?(c)(-/-) mice injected with HS1-silenced CLL B cells showed a decreased organ infiltration with the notable exception of the bone marrow (BM). The leukemic-prone E?-TCL1 transgenic mice crossed with HS1-deficient mice were compared with E?-TCL1 mice and showed an earlier disease onset and a reduced survival. These findings show that HS1 is a central regulator of cytoskeleton remodeling that controls lymphocyte trafficking and homing and significantly influences the tissue invasion and infiltration in CLL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3537-46
pubmed:meshHeading
pubmed-meshheading:20530793-Actins, pubmed-meshheading:20530793-Adaptor Proteins, Signal Transducing, pubmed-meshheading:20530793-Animals, pubmed-meshheading:20530793-B-Lymphocytes, pubmed-meshheading:20530793-Blood Proteins, pubmed-meshheading:20530793-Bone Marrow, pubmed-meshheading:20530793-Cell Adhesion, pubmed-meshheading:20530793-Cell Line, Tumor, pubmed-meshheading:20530793-Cell Movement, pubmed-meshheading:20530793-Cytoskeleton, pubmed-meshheading:20530793-DNA-Binding Proteins, pubmed-meshheading:20530793-Gene Expression Regulation, Leukemic, pubmed-meshheading:20530793-Gene Silencing, pubmed-meshheading:20530793-Humans, pubmed-meshheading:20530793-Leukemia, Lymphocytic, Chronic, B-Cell, pubmed-meshheading:20530793-Male, pubmed-meshheading:20530793-Mice, pubmed-meshheading:20530793-Mice, Inbred BALB C, pubmed-meshheading:20530793-Mice, Inbred C57BL, pubmed-meshheading:20530793-Mice, Transgenic, pubmed-meshheading:20530793-Tumor Cells, Cultured
pubmed:year
2010
pubmed:articleTitle
HS1 has a central role in the trafficking and homing of leukemic B cells.
pubmed:affiliation
Unit of Lymphoid Malignancies, Division of Molecular Oncology, San Raffaele Scientific Institute, Via Olgettina 58, Milan, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't