HS1 has a central role in the trafficking and homing of leukemic B cells.
Blood
; 116(18): 3537-46, 2010 Nov 04.
Article
em En
| MEDLINE
| ID: mdl-20530793
ABSTRACT
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(-/-)γ(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 Eµ-TCL1 transgenic mice crossed with HS1-deficient mice were compared with Eµ-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Sanguíneas
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Linfócitos B
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Leucemia Linfocítica Crônica de Células B
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Movimento Celular
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas de Ligação a DNA
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article