Purpose: Blastic NK cell lymphoma/blastic plasmacytoid dendritic cell neoplasm (BNKL) is a rare and aggressive neoplasia characterized by infiltration of blast CD4+/CD56+ cells in the skin, the bone marrow (BM) and in the peripheral blood (PB). Currently, more efforts are required to better define molecular and biological mechanisms associated to this pathology. To the best of our knowledge, no mouse model recapitulated human BNKL so far. Experimental Design: Primary BM cells from a BNKL patient were injected in NOD SCID IL2rγ-/- mice with the intent to generate the first BNKL orthotopic mouse model. Moreover, because of the lack of efficient treatments for BNKL, we treated mice with lenalidomide, an immunomodulatory and antiangiogenic drug. Results: We generated in mice a fatal disease resembling well human BNKL. After lenalidomide treatment, we observed a significant reduction in the number of PB, BM and spleen BNKL cells. Tumor reduction parallels with a significant decrease in the number of circulating endothelial (CECs) and progenitors cells (CEPs), and CD31+ murine endothelial cells. In mice treated with lenalidomide, BNKL levels of active Caspase-3 were significantly augmented, thus demonstrating proapoptotic and cytotoxic effects of this drug in vivo. An opposite result was found for PCNA, a proliferation marker. Conclusions: Our BNKL model might better define the cellular and molecular mechanisms involved in this disease, and lenalidomide might be considered for the future therapy of BNKL patients.
- Received January 25, 2011.
- Revision received June 28, 2011.
- Accepted August 8, 2011.
- Copyright © 2011, American Association for Cancer Research.