The Rho GTPase Network in anaplastic large cell lymphoma: From Lymphomagenesis to Therapeutic Targeting.
Claudia Voena
University of Torino, Italy
Anaplastic large cell lymphoma (ALCL), particularly the ALK+ subtype, is driven by constitutive oncogenic kinase signaling that sustains tumor growth and survival. Beyond tumor-intrinsic oncogenic drivers, increasing evidence suggests that cytoskeletal dynamics and cell– microenvironment interactions play critical roles in lymphoma persistence. Members of the Rho family of small GTPases—including RHOA, RAC1, and CDC42—are central regulators of actin remodeling, cell migration, anchorage, and survival signaling.
Our recent Sindings show that RHOA is essential for ALK+ ALCL development and maintenance.
Its loss disrupts cytoskeletal organization, impairs lymphoma growth, and sensitizes tumors to ALK inhibition, revealing a key dependency on Rho GTPase activity. Together with our previously published studies on CDC42 and RAC1, these Sindings support a model in which Rho family GTPases function as integrators of oncogenic ALK signaling. Overall, our Sindings highlight Rho GTPase networks as central regulators of T-cell lymphoma biology, unveiling new therapeutic strategies targeting cytoskeletal signaling programs across ALCL.