The project investigates the therapeutic value of WASP — a hematopoietic-restricted regulator of actin cytoskeleton dynamics — in myeloproliferative neoplasms (MPN). WASP governs hematopoietic cell proliferation, migration, homing, and bone marrow retention, and operates independently of oncogenic JAK-STAT signaling, the canonical driver of MPN pathogenesis. This mechanistic independence positions WASP as a distinct and unexplored therapeutic target with synergistic potential alongside current MPN therapies, including tyrosine kinase inhibitors (TKIs) and interferon-alpha (IFNα). Translational relevance extends beyond MPN, as niche-mediated therapeutic resistance is a broader challenge in hematological and solid malignancies.