CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells.

CD137 ligand ( CD137 L), a member of the tumour necrosis factor family, is expressed as a cell surface molecule. Engagement of CD137 L on haematopoietic progenitor cells induces monocytic differentiation, and in peripheral monocytes CD137 L signalling promotes differentiation to mature dendritic cells. We hypothesized that CD137 L signalling would also induce differentiation in transformed myeloid cells. Here we show that recombinant CD137 protein, which crosslinks CD137L and initiates reverse CD137 L 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 CD137 L 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. CD137 L 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. [ABSTRACT FROM AUTHOR]