TY - JOUR
T1 - HS1 has a central role in the trafficking and homing of leukemic B cells
AU - Scielzo, Cristina
AU - Bertilaccio, Maria T.S.
AU - Simonetti, Giorgia
AU - Dagklis, Antonis
AU - Ten Hacken, Elisa
AU - Fazi, Claudia
AU - Muzio, Marta
AU - Caiolfa, Valeria
AU - Kitamura, Daisuke
AU - Restuccia, Umberto
AU - Bachi, Angela
AU - Rocchi, Martina
AU - Ponzoni, Maurilio
AU - Ghia, Paolo
AU - Caligaris-Cappio, Federico
PY - 2010/11/4
Y1 - 2010/11/4
N2 - 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-/-γc-/- 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.
AB - 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-/-γc-/- 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.
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U2 - 10.1182/blood-2009-12-258814
DO - 10.1182/blood-2009-12-258814
M3 - Article
C2 - 20530793
AN - SCOPUS:78149309123
SN - 0006-4971
VL - 116
SP - 3537
EP - 3546
JO - Blood
JF - Blood
IS - 18
ER -