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Involvement of Gpr125 in the myeloid sarcoma formation induced by cooperating MLL/AF10(OM‐LZ) and oncogenic KRAS in a mouse bone marrow transplantation model
Author(s) -
Fu JenFen,
Yen TzungHai,
Chen Yu,
Huang YingJung,
Hsu ChengLung,
Liang DerCherng,
Shih LeeYung
Publication year - 2013
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.28195
Subject(s) - kras , cancer research , myeloid , myeloid sarcoma , bone marrow , myeloid leukemia , biology , downregulation and upregulation , microbiology and biotechnology , immunology , cancer , genetics , colorectal cancer , gene
Oncogenic N‐/KRAS mutations were frequently associated with MLL/AF10 in acute myeloid leukemia with myeloid sarcoma (MS). To study the cooperating leukemogenesis by MLL/AF10 and KRAS mutation, we retrovirally transduced MLL/AF10(OM‐LZ) and KRAS G12C into mouse bone marrow cells and generated two immortalized cell lines. The cells carrying cooperating MLL/AF10(OM‐LZ) and KRAS G12C had immature myelomonocytic phenotypes. Compared to a previously established cell line carrying MLL/AF10(OM‐LZ) alone, cooperation of MLL/AF10(OM‐LZ) with KRAS G12C blocked the cells at a more immature myelomonocytic stage with reduced expression of monocyte/macrophage markers. The mice transplanted with the cells carrying cooperating MLL/AF10(OM‐LZ) and KRAS G12C , liked those transplanted with the cells carrying MLL/AF10(OM‐LZ) alone, induced myeloproliferative disease‐like myeloid leukemia, but in a shorter latency and formed multiple MS at the adipose tissues of skin, peritoneum and intraperitoneal cavity. Cooperation of MLL/AF10(OM‐LZ) with KRAS G12C increased cell adhesion via upregulation of an adhesion G‐protein‐coupled receptor Gpr125 . Knockdown of Gpr125 in the cells by short hairpin RNA reduced cell aggregation and diminished MS formation in the transplanted mice. Our results indicated that upregulation of Gpr125 by cooperating MLL/AF10(OM‐LZ) and KRAS G12C promoted cell adhesion and contributed to the MS formation.