G-protein coupled receptor kinase-2 regulates the migration of chronic lymphocytic leukaemia cells to sphingosine-1 phosphate in vitro and their trafficking in vivo.

ABSTRACT: Disease progression and drug resistance in patients with chronic lymphocytic leukaemia (CLL) depend on signals from the tumour microenvironment in lymphoid sites. GRK2 inhibits the egress of normal B cells from lymphoid tissues by inducing the downregulation of the S1P-receptor 1 (S1PR1). In this study we investigated the role of GRK2 in the context of CLL using in vitro and in vivo murine models, and also primary samples from CLL patients. We found that pharmacological inhibition of GRK2 enhanced the migration of leukemic cells from CLL patients towards S1P and impaired the S1P-induced downregulation of S1PR1. Likewise, CRISPR/Cas9-mediated GRK2 deletion in a murine leukemic cell line derived from the Eµ-TCL1 mouse model of CLL also increased migratory capacity toward S1P in vitro. Furthe

SUBMITTER: Cassarino MC 

PROVIDER: S-EPMC11847938 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature