B cell acute lymphoblastic leukemia cells mediate RANK-RANKL–dependent bone destruction
Sujeetha A. Rajakumar(University of Toronto), Eniko Papp(University of Toronto), Kathy K. Lee(University of Toronto), Ildiko Grandal(Hospital for Sick Children), Daniele Merico(Hospital for Sick Children), Careesa C. Liu(University of Toronto), Bedilu Allo(Lunenfeld-Tanenbaum Research Institute), Lucia Zhang(University of Toronto), Marc D. Grynpas(University of Toronto), Mark D. Minden(University Health Network), Johann Hitzler(Hospital for Sick Children), Cynthia J. Guidos(University of Toronto), Jayne S. Danska(University of Toronto)
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Abstract
/SzJ (NSG) recipient mice. Primary B-ALL cells conferred bone destruction evident in increased multinucleated osteoclasts, trabecular bone loss, destruction of the metaphyseal growth plate, and reduction in adipocyte mass in these patient-derived xenografts (PDXs). Treating PDX mice with the RANKL antagonist recombinant osteoprotegerin-Fc (rOPG-Fc) protected the bone from B-ALL-induced destruction even under conditions of heavy tumor burden. Our data demonstrate a critical role of the RANK-RANKL axis in causing B-ALL-mediated bone pathology and provide preclinical support for RANKL-targeted therapy trials to reduce acute and long-term bone destruction in these patients.
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