WASp signaling in T-cell lymphomas

ABSTRACT Title: WASp signaling in T-cell lymphomas Peripheral T-cell lymphomas (PTCL) are aggressive disorders, with less than 50% overall survival after 2-3 years of diagnosis. These dismal outcomes are in no small part secondary to the limited number of available biomarkers of disease progression and the limited knowledge of T-cell lymphoma biology. Emergent evidence indicates that the actin cytoskeleton plays a pivotal role during T-cell lymphomas' development and growth; however, actin-related proteins' role as actionable targets in T-cell lymphomas still needs to be defined. Our preliminary findings demonstrate that the actin regulatory protein Wiskott-Aldrich syndrome protein (WASp) is associated with decreased event-free survival and promotes T-cell lymphoma growth and survival. In this proposal, we will leverage a genetically engineered murine (GEM) model that develops spontaneous peripheral T-cell lymphomas (SNF5FL/CD4cre), and we will capitalize on an international consortium of more than 100 T-cell lymphoma cases collected with accompanying annotated clinical outcomes, to test the role of WASp during the assembly of actin-dependent signaling complexes upstream of oncogenic transcriptional signaling, and define the role of the tumor microenvironment driving WASp-dependent oncogenic signaling.