Autocrine Signaling by Wnt-5a Deregulates Chemotaxis of Leukemic Cells and Predicts Clinical Outcome in Chronic Lymphocytic Leukemia.
|Druh||Článek v odborném periodiku|
|Časopis / Zdroj||Clinical cancer research|
|Fakulta / Pracoviště MU|
|Obor||Genetika a molekulární biologie|
|Klíčová slova||ROR1; Wnt/PCP pathway; CLLB cells|
|Popis||Chronic lymphocytic leukemia (CLL) is the most common leukemia diagnosed in the Western world. Despite increased understanding of the disease biology and better risk stratification, the disease is still considered incurable. In the current study, we provide evidence that CLL cells with positive expression of WNT5A, encoding ligand for the surface receptor ROR1 uniformly upregulated in CLL, define the subgroup of patients with poor prognosis. The most aggressive CLL cases with dysfunctional p53 and mutated SF3B1 are enriched with WNT5A-positive cells, independently of their IGHV mutational status. Functional data show that WNT5A-positive CLL cells have increased motility and deregulated chemotactic responses due to Wnt-5a autocrine signaling. In summary, our data identify WNT5A expression as a new, stable, and strong marker of time to first treatment. Moreover, altered migration properties of WNT5A-positive patient cohort further substantiate the clinical importance of the interaction of CLL cells with their microenvironment.|