CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells
Kin Cheng
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Search for more papers by this authorSiew Cheng Wong
Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR), Singapore City, Singapore
Search for more papers by this authorYeh Ching Linn
Department of Haematology, Singapore General Hospital, Singapore City, Singapore
Search for more papers by this authorLiam Pock Ho
Department of Haematology, Singapore General Hospital, Singapore City, Singapore
Search for more papers by this authorWee Joo Chng
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore
Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore City, Singapore
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore City, Singapore
Search for more papers by this authorCorresponding Author
Herbert Schwarz
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore City, Singapore
Correspondence: Herbert Schwarz, Department of Physiology, National University of Singapore, MD9, 2 Medical Drive, Singapore City 117597, Singapore.
E-mail: [email protected]
Search for more papers by this authorKin Cheng
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Search for more papers by this authorSiew Cheng Wong
Singapore Immunology Network, Agency for Science, Technology and Research (ASTAR), Singapore City, Singapore
Search for more papers by this authorYeh Ching Linn
Department of Haematology, Singapore General Hospital, Singapore City, Singapore
Search for more papers by this authorLiam Pock Ho
Department of Haematology, Singapore General Hospital, Singapore City, Singapore
Search for more papers by this authorWee Joo Chng
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Cancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore
Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore City, Singapore
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore City, Singapore
Search for more papers by this authorCorresponding Author
Herbert Schwarz
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore City, Singapore
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore City, Singapore
Correspondence: Herbert Schwarz, Department of Physiology, National University of Singapore, MD9, 2 Medical Drive, Singapore City 117597, Singapore.
E-mail: [email protected]
Search for more papers by this authorSummary
CD137 ligand (CD137L), a member of the tumour necrosis factor family, is expressed as a cell surface molecule. Engagement of CD137L on haematopoietic progenitor cells induces monocytic differentiation, and in peripheral monocytes CD137L signalling promotes differentiation to mature dendritic cells. We hypothesized that CD137L signalling would also induce differentiation in transformed myeloid cells. Here we show that recombinant CD137 protein, which crosslinks CD137L and initiates reverse CD137L signalling in myeloid cells, induces morphological changes (adherence, spreading), loss of progenitor markers (CD117), expression of maturation markers (CD11b, CD13) and secretion of cytokines that are indicative of myeloid differentiation. Under the influence of CD137L signalling, acute myeloid leukaemia (AML) cells acquired expression of co-stimulatory molecules (CD80, CD86, CD40), the dendritic cell marker CD83 and dendritic cell activities, enabling them to stimulate T cells. CD137L signalling induced differentiation in 71% (15 of 21) of AML samples, irrespective of French-American-British classification and CD137L expression level. However, the type of response varied with the AML subtype and patient sample. In summary, this study demonstrated that CD137L signalling induced differentiation in malignant cells of AML patients, and suggests that it may be worthwhile to investigate treatment with recombinant CD137 protein as a potential novel therapeutic approach for AML.
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