title: Upregulation of CD200R1 in lineage-negative leukemic cells is characteristic of AML1-ETO-positive leukemia in mice.
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-Kit(D814V) 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-Kit(D814V), AML1(D171N), and AML1(S291fsX300). 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.
authors.affiliation: 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.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kagiyama
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Togami
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Uchida
authors.forename: Daichi
authors.initials: D
authors.lastname: Inoue
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Matsukawa
authors.forename: Kumi
authors.initials: K
authors.lastname: Izawa
authors.forename: Kimihito C
authors.initials: KC
authors.lastname: Kawabata
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Komeno
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Oki
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakahara
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D007938:Leukemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020125:Mutation, Missense; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D064446:Orexin Receptors; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000954:Antigens, Surface; C501103:Cd200r1 protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C493598:MTG8 protein, mouse; D015514:Oncogene Proteins, Fusion; D064446:Orexin Receptors; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit