| Literature DB >> 29868798 |
Nathaniel J Buteyn1, Kavin Fatehchand2, Ramasamy Santhanam3, Huiqing Fang3, Gino M Dettorre3, Shalini Gautam3, Bonnie K Harrington4, Sally E Henderson4, Giovanna Merchand-Reyes1, Xiaokui Mo5, Don M Benson3, William E Carson3, Sumithira Vasu3, John C Byrd3, Jonathan P Butchar3, Susheela Tridandapani3.
Abstract
Acute myeloid leukemia (AML) remains a significant health problem, with poor outcomes despite chemotherapy and bone marrow transplants. Although one form of AML, acute promyelocytic leukemia (APL), is successfully treated with all-trans retinoic acid (ATRA), this drug is seemingly ineffective against all other forms of AML. Here, we show that ATRA up-regulates CD38 expression on AML blasts to sufficient levels that promote antibody-mediated fratricide following the addition of anti-CD38 daratumumab (DARA). The combination of ATRA plus DARA induced Fc-dependent conjugate formation and cytotoxicity among AML blasts in vitro. Combination treatment also led to reduction in tumor volume and resulted in increased overall survival in murine engraftment models of AML. These results suggest that, although ATRA does not induce differentiation of non-APL, it may be effective as a therapy in conjunction with DARA.Entities:
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Year: 2018 PMID： 29868798 PMCID： PMC6059202 DOI： 10.1093/intimm/dxy040
Source DB: PubMed Journal: Int Immunol ISSN： 0953-8178 Impact factor: 5.071