Intrathymic Notch3 and CXCR4 combinatorial interplay facilitates T-cell leukemia propagation.

ABSTRACT: Notch hyperactivation dominates T-cell acute lymphoblastic leukemia development, but the mechanisms underlying "pre-leukemic" cell dissemination are still unclear. Here we describe how deregulated Notch3 signaling enhances CXCR4 cell-surface expression and migratory ability of CD4⁺CD8⁺ thymocytes, possibly contributing to "pre-leukemic" cell propagation, early in disease progression. In transgenic mice overexpressing the constitutively active Notch3 intracellular domain, we detect the progressive increase in circulating blood and bone marrow of CD4⁺CD8⁺ cells, characterized by high and combined surface expression of Notch3 and CXCR4. We report for the first time that transplantation of such CD4⁺CD8⁺ cells reveals their compe

SUBMITTER: Ferrandino F 

PROVIDER: S-EPMC6284016 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature