HS1 has a central role in the trafficking and homing of leukemic B cells

Cristina Scielzo, Maria T S Bertilaccio, Giorgia Simonetti, Antonis Dagklis, Elisa Ten Hacken, Claudia Fazi, Marta Muzio, Valeria Caiolfa, Daisuke Kitamura, Umberto Restuccia, Angela Bachi, Martina Rocchi, Maurilio Ponzoni, Paolo Ghia, Federico Caligaris-Cappio

Research output: Contribution to journalArticlepeer-review

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-/-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.

Original languageEnglish
Pages (from-to)3537-3546
Number of pages10
JournalBlood
Volume116
Issue number18
DOIs
Publication statusPublished - Nov 4 2010

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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