title: CD137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Kin
authors.initials: K
authors.lastname: Cheng
authors.forename: Siew Cheng
authors.initials: SC
authors.lastname: Wong
authors.forename: Yeh Ching
authors.initials: YC
authors.lastname: Linn
authors.forename: Liam Pock
authors.initials: LP
authors.lastname: Ho
authors.forename: Wee Joo
authors.initials: WJ
authors.lastname: Chng
authors.forename: Herbert
authors.initials: H
authors.lastname: Schwarz
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000378:metabolism*; D008875:Middle Aged; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism; D055815:Young Adult
chemical_list: D053330:4-1BB Ligand; D015703:Antigens, CD; D011993:Recombinant Fusion Proteins; C505974:TNFSF9 protein, human; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9
keywords: CD137; acute myeloid leukaemia; dendritic cell; differentiation