Summary
The c-fms protooncogene encodes the receptor for the colony-stimulating factor 1 of macrophages. Its transforming counterpart, the v-fms oncogene has previously been recognized as the transforming gene of the McDonough strain of feline sarcoma virus. We have isolated rabbit antisera against a 115-kDa recombinant polypeptide containing the 926 carboxy-terminal amino acids of the v-fms protein. All antibodies recognized the cytoplasmic domain of the v-fms protein, which is 95% homologous to the corresponding domain of human c-fms proteins. These sera were applied in a survey of various human cancer cell lines, such as peripheral blood mononuclear (HL60) and choriocarcinoma (BeWo) cells, as well as leukemic cells from 58 patients with acute myelocytic, chronic myelocytic or acute lymphocytic leukemias (AML, CML, ALL). Significantly enhanced levels of fms-specific tyrosine kinase activity were detected in 12-O-tetradecanoylphorbol-13-acetate-induced HL60 and in BeWo cells, and in 7 out of 24 samples from AML patients, whereas no activity could be detected in 9 ALL or in 25 CML cell preparations. The AML cells were classified according to the FAB criteria. The highest incidence of increased fms activity was found in cells assigned to the M4 class (four out of five cases). While no activity was found in material belonging to FAB classes M2 or M3, one of the two cases of the M5 class was kinase-positive. Interestingly, two out of seven cases of the M1 class cells exhibited enhanced levels of fms kinase. These data suggest that the determination of the fms kinase may be useful to subdivide the M1 class of the FAB classification into monocytic and non-monocytic precursor leukemia cells.
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Abbreviations
- ALL:
-
acute lymphocytic leukemia
- AML:
-
acute myelocytic leukemia
- CML:
-
chronic myelocytic leukemia
- FAB classification:
-
French-American-Britisch classification
- SM-FeSV:
-
McDonough strain of feline leukemia virus
- M-CSF (CSF-1):
-
colony-stimulating factor 1 of macrophages
- SDS-PAGE:
-
sodium dodecyl sulfate/polyacrylamide gel electrophoresis
- TBR sera:
-
tumorbearing rat sera
- TPA:
-
12-O-tetradecanoylphorbol 13-acetate
References
Bennett JM, Catovsky D, Daniel M-T, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of acute leukaemias. Br J Haematol 33:451–458
Bennett JM, Catovsky D, Daniel MT, Flandrini G, Galton AG, Gralnick HR, Sultan C (1985) Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 103:626–629
Cayre Y, Raynal M-C, Darzynkiewicz Z, Dorner MH (1987) Model for intermediate steps in monocytic differentiation: c-myc, c-fms, and ferritin as markers. Proc Natl Acad Sci USA 84:7619–7623
Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM, Ullrich A (1986) Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature 320:277–280
Hadwiger G, Niemann H, Käbisch A, Bauer H, Tamura T (1986) Appropriate glycosylation of the fms gene product is a prerequisite for its transforming potency. EMBO J 5:689–694
Hampe A, Gobert M, Sherr CJ, Galibert F (1984) Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. Proc Natl Acad Sci USA 81:85–89
Horiguchi J, Sherman ML, Sampson-Johannes A, Weber BL, Kufe DW (1988) CSF-1 and c-fms gene expression in human carcinoma cell lines. Biochem Biophys Res Commun 157:395–401
LeBeau MM, Westbrook CA, Diaz MO, Larson RA, Rowley JD, Gasson JC, Golde DW, Sherr CJ (1986) Evidence for the involvement of GM-CSF and fms in the deletion (5q) in myeloid disorders. Science 231:984–987
Müller R, Salmon DJ, Adamson ED, Tremblay JM, Müller D, Cline MJ, Verma IM (1983) Transcription of c-onc genes c-ras and c-fms during mouse development. Mol Cell Biol 3:1062–1069
Nienhuis AW, Bunn HF, Turner PH, Gopal TV, Nash WG, O'Brien SJ, Sherr CJ (1985) Expression of the human c-fms proto-oncogene in hematopoetic cells and its deletion in the 5q- syndrome. Cell 42:421–428
Preisler HD, Kinniburgh AJ, Wei-Dong G, Khan S (1987) Expression of the protooncogenes c-myc, c-fos, and c-fms in acute myelocytic leukemia at diagnosis and in remission. Cancer Res 47:874–880
Rambaldi A, Wakamiya N, Vellenga E, Horiguchi J, Warren MK, Kufe D, Griffin JD (1988) Expression of the macrophage colony-stimulating factor and c-fms genes in human acute myeloblastic leukemia cells. J Clin Invest 81:1030–1035
Rettenmier CW, Sacca R, Furman WL, Roussel MF, Holt JT, Nienhuis AW, Stanley ER, Sherr CJ (1986) Expression of the human c-fms protooncogene product (colony-stimulating factor-1 receptor) on peripheral blood mononuclear cells and choriocarcinoma cell lines. J Clin Invest 77:1740–1746
Sariban E, Mitchell T, Kufe D (1985) Expression of the c-fms protooncogene during human monocytic differentiation. Nature 316:64–66
Sherr C-J, Rettenmier CW, Sacca R, Roussel MF, Look AT, Stanley ER (1985) The c-fms proto-oncogene product is related to the receptor for the mononuclear phagocyte growth factor, CSF-1. Cell 41:665–676
Strebel K, Beck E, Strohmaier K, Schaller H (1986) Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins. J Virol 57:983–991
Tamura T, Bauer H, Birr C, Pipkorn R (1983) Antibodies against synthetic peptides as a tool for functional analysis of the transforming protein pp60src. Cell 34:587–596
Tamura T, Simon E, Niemann H, Snoek GT, Bauer H (1986) SM-FeSV gp140v-fms molecules expressed at the cell surface are phosphorylated in tyrosine and serine. Mol Cell Biol 6:4745–4748
Wheeler EF, Rettenmier CW, Look AT, Sherr CJ (1986) The v-fms oncogene induces factor independence and tumorigenicity in CSF-1 dependent macrophage cell line. Nature 324:377–380
Wheeler EF, Askew D, May S, Ihle JN, Sherr CJ (1987) The v-fms oncogene induces factor-independent growth and transformation of the interleukin-3-dependent myeloid cell line FDC-P1. Mol Cell Biol 7:1673–1680
Woolford J, Rothwell V, Rohrschneider L (1985) Characterization of the human c-fms gene product and its expression in cells of the monocyte-macrophage lineage. Mol Cell Biol 5:3458–3466
Woolford J, McAuliffe A, Rohrschneider L (1988) Activation of the feline c-fms proto-oncogene: multiple alterations are required to generate a fully transformed phenotype. Cell 55:965–977
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Tamura, T., Brost, H., Käbisch, A. et al. Detection of fms-oncogene-specific tyrosine kinase activity in human leukemia cells. J Cancer Res Clin Oncol 115, 235–241 (1989). https://doi.org/10.1007/BF00391695
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DOI: https://doi.org/10.1007/BF00391695