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Upregulation of CD200R1 in lineage-negative leukemic cells is characteristic of AML1-ETO-positive leukemia in mice

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Abstract

Activating mutations of c-Kit are frequently found in acute myeloid leukemia (AML) patients harboring t(8;21) chromosomal translocation generating a fusion protein AML1-ETO. Here we show that an active mutant of c-Kit cooperates with AML1-ETO to induce AML in mouse bone marrow transplantation models. Leukemic cells expressing AML1-ETO with c-KitD814V were serially transplantable. Transplantation experiments indicated that lineage−c-Kit+Sca-1+ (KSL) leukemic cells, but not lineage+ leukemic cells, were enriched for leukemia stem cells (LSCs). Comparison of gene expression profiles between KSL leukemic and normal cells delineated that CD200R1 was highly expressed in KSL leukemic cells as compared with KSL normal cells. Upregulation of CD200R1 was verified in lineage− leukemic cells, but not in lineage+ leukemic cells. CD200R1 expression in the lineage− leukemic cells was not correlated with the frequency of LSCs, indicating that CD200R1 is not a useful marker for LSCs in these models. Interestingly, CD200R1 was upregulated in KSL cells transduced with AML1-ETO, but not with other leukemogenic mutants, including c-KitD814V, AML1D171N, and AML1S291fsX300. Consistently, upregulation of CD200R1 in lineage− leukemic cells was observed only in the BM of mice suffering from AML1-ETO-positive leukemia. In conclusion, AML1-ETO upregulated CD200R1 in lineage− cells, which was characteristic of AML1-ETO-positive leukemia in mice.

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Acknowledgments

We thank Drs. Issay Kitabayashi and Yuzuru Kanakura for kindly providing plasmids. This work was supported by Grants-in-aid for Scientific Research on Innovative Areas, MEXT, Japan and Grants-in-aid for Scientific Research (A), JSPS, Japan.

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Authors and Affiliations

  1. Division of Cellular Therapy, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Yuki Kagiyama, Jiro Kitaura, Katsuhiro Togami, Tomoyuki Uchida, Daichi Inoue, Toshihiro Matsukawa, Kumi Izawa, Kimihito C. Kawabata, Yukiko Komeno, Toshihiko Oki, Fumio Nakahara & Toshio Kitamura

  2. Division of Stem Cell Signaling, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Toshihiko Oki & Toshio Kitamura

  3. Laboratory for Dendritic Cell Immunobiology and Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan

    Katsuaki Sato

  4. Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan

    Hiroyuki Aburatani

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  1. Yuki Kagiyama
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Correspondence to Toshio Kitamura.

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Kagiyama, Y., Kitaura, J., Togami, K. et al. Upregulation of CD200R1 in lineage-negative leukemic cells is characteristic of AML1-ETO-positive leukemia in mice. Int J Hematol 96, 638–648 (2012). https://doi.org/10.1007/s12185-012-1207-6

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  • DOI: https://doi.org/10.1007/s12185-012-1207-6

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