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CD 137 ligand signalling induces differentiation of primary acute myeloid leukaemia cells
Author(s) -
Cheng Kin,
Wong Siew Cheng,
Linn Yeh Ching,
Ho Liam Pock,
Chng Wee Joo,
Schwarz Herbert
Publication year - 2014
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12732
Subject(s) - cd40 , myeloid , biology , cd80 , haematopoiesis , cellular differentiation , immunology , progenitor cell , cd86 , microbiology and biotechnology , stem cell , cancer research , t cell , immune system , cytotoxic t cell , in vitro , biochemistry , gene
Summary CD 137 ligand ( CD 137 L ), a member of the tumour necrosis factor family, is expressed as a cell surface molecule. Engagement of CD 137 L on haematopoietic progenitor cells induces monocytic differentiation, and in peripheral monocytes CD 137 L signalling promotes differentiation to mature dendritic cells. We hypothesized that CD 137 L signalling would also induce differentiation in transformed myeloid cells. Here we show that recombinant CD 137 protein, which crosslinks CD 137L and initiates reverse CD 137 L signalling in myeloid cells, induces morphological changes (adherence, spreading), loss of progenitor markers ( CD 117), expression of maturation markers ( CD 11b, CD 13) and secretion of cytokines that are indicative of myeloid differentiation. Under the influence of CD 137 L signalling, acute myeloid leukaemia ( AML ) cells acquired expression of co‐stimulatory molecules ( CD 80, CD 86, CD 40), the dendritic cell marker CD 83 and dendritic cell activities, enabling them to stimulate T cells. CD 137 L signalling induced differentiation in 71% (15 of 21) of AML samples, irrespective of F rench‐ A merican‐ B ritish classification and CD 137L expression level. However, the type of response varied with the AML subtype and patient sample. In summary, this study demonstrated that CD 137L signalling induced differentiation in malignant cells of AML patients, and suggests that it may be worthwhile to investigate treatment with recombinant CD 137 protein as a potential novel therapeutic approach for AML .