Implication of expression of GDNF/Ret signalling components in differentiation of bone marrow haemopoietic cells

Seiko Nakayama, Ken Ichi Iida, Toyonori Tsuzuki, Toshihide Iwasiiita, Hideki Murakami, Naoya Asai, Yosuke Iwata, Masatoshi Ichihara, Shinji Ito, Kumi Kawai, Masami Asai, Ivei Kurokawa, Masahide Takahashi

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19 Citations (Scopus)


Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) mediate their actions through a unique multicomponent receptor system composed of Ret receptor tyrosine kinase and glycosyl-phosphatidylinositol- linked cell surface proteins (designated GFRα-1 and GFRα-2). In the present study, expression of these signalling components in the process of differentiation of haemopoietic cells was investigated. Ret was expressed at variable levels in normal and malignant cells of the myelomonocyte lineage. Immunohistochemical analysis of human and mouse tissues revealed that Ret expression was increased in intermediate mature myeloid cells such as promyelocytes and myelocytes and decreased in mature granulocytes and monocytes. Consistent with this observation, when THP-1 monocytic and HL-60 promyelocytic leukaemia cells expressing Ret were differentiated toward macrophages or granulocytes by treatment of 12-O-tetradecanoylphorbol-13- acetate (TPA) or all-trans retinoic acid (RA), Ret expression strikingly decreased during differentiation. Expression of GDNF, NTN, GFRα-1 and GFRα- 2 was undetectable in HP-1 and HL-60 cells as well as in bone marrow haemopoietic cells. In contrast, bone marrow stromal cells appeared to express GDNF, GFRα-1 and GFRα-2 but not Ret. These findings suggested that the interaction between stromal cells and Ret-expressing haemopoietic cells in the bone marrow microenvironment may play a role in the differentiation of myelomonocyte-lineage cells through activation of the GDNF/Ret signalling pathway.

Original languageEnglish
Pages (from-to)50-57
Number of pages8
JournalBritish Journal of Haematology
Issue number1
Publication statusPublished - 1999

All Science Journal Classification (ASJC) codes

  • Hematology


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