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Quelle: Bohlander 2005 Seite(n): 163, 164, 165, Zeilen: 163: r.col: 32ff; 164: l.col: 1ff; 165: r.col: 1ff |
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| [The fusion protein critical for the development of the chronic myelo-]monocytic leukemia is the ETV6/PDGFRB fusion and not the reciprocal PDGFRB/ETV6 fusion. In the ETV6/PDGFRB fusion protein the N terminal portion of ETV6, which includes the pointed domain, is fused to the C-terminal two thirds of the PDGFRB protein, conserving the tyrosine kinase domain of PDGFRB. The fusion of the pointed domain of ETV6 in the N-terminal half with the tyrosine kinase domain in the C-terminal half of the fusion partner is characteristic of the class of ETV6/PTK fusions and is found in the fusions of ETV6 with ABL1, ABL2, JAK2, NTRK3, FGFR3 and SYK (Fig. 11) (Table 2) (Papadopoulos et. al., 1995; Cazzaniga et. al., 1999; Knezevich et. al., 1998; Kuno et. al., 2001; Peeters et. al., 1997)
Table2. Tyrosine kinase fusion partners of ETV6
1.6.4 Transcription factors and other fusion partners of ETV6 The ETV6/RUNX1 (ETV6/AML1) fusion is the most common fusion gene in childhood acute B cell lymphoblastic leukemia (Shurtleff et. al., 1995). Cazzaniga, G., Tosi, S., Aloisi, A., Giudici, G., Daniotti, M., Pioltelli, P., Kearney, L., and Biondi, A. (1999). The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. Blood 94, 4370- 4373. Knezevich, S. R., McFadden, D. E., Tao, W., Lim, J. F., and Sorensen, P. H. (1998). A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 18, 184-187. Kuno, Y., Abe, A., Emi, N., Iida, M., Yokozawa, T., Towatari, M., Tanimoto, M., and Saito, H. (2001). Constitutive kinase activation of the TEL-Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). Blood 97, 1050-1055. Papadopoulos, P., Ridge, S. A., Boucher, C. A., Stocking, C., and Wiedemann, L. M. (1995). The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 55, 34-38. Peeters, P., Raynaud, S. D., Cools, J., Wlodarska, I., Grosgeorge, J., Philip, P., Monpoux, F., Van Rompaey, L., Baens, M., Van den Berghe, H., and Marynen, P. (1997a). Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 90, 2535- 2540. Peeters, P., Wlodarska, I., Baens, M., Criel, A., Selleslag, D., Hagemeijer, A., Van den Berghe, H., and Marynen, P. (1997b). Fusion of ETV6 to MDS1/EVI1 as a result of t(3;12)(q26;p13) in myeloproliferative disorders. Cancer Res 57, 564-569. Shurtleff, S. A., Buijs, A., Behm, F. G., Rubnitz, J. E., Raimondi, S. C., Hancock, M. L., Chan, G. C., Pui, C. H., Grosveld, G., and Downing, J. R. (1995). TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 9, 1985-1989. |
The fusion protein that is critical for the development of the chronic myelomonocytic leukemia and that has shown considerable transformation potential in cell line assays is the ETV6/PDGFRB fusion and not the reciprocal PDGFRB/ETV6 fusion. In the ETV6/PDGFRB fusion protein, the N-terminal portion of ETV6, which includes the pointed domain is fused to the C-terminal two-thirds of the PDGFRB protein, which includes the tyrosine kinase domain of PDGFRB. This general structure, i.e. pointed domain of ETV6 in the N-terminal half and tyrosine kinase domain in
[page 164] the C-terminal half of the fusion protein, is characteristic of ETV6/PTK fusions and is found in the fusions of ETV6 to ABL1, ABL2, JAK2, NTRK3, FGFR3 and SYK (see Table 1 and Fig. 1) [11–18]. Table 1 Protein tyrosine kinase fusion partners of ETV6
[page 165] 6. Transcription factors and other fusion partners of ETV6 [...] Shortly after its discovery, the ETV6/RUNX1 fusion was recognized to be the most common fusion gene found in childhood acute B cell lymphoblastic leukemia [39]. [11] Papadopoulos P, Ridge SA, Boucher CA, Stocking C, Wiedemann LM. The novel activation of ABL by fusion to an ets-related gene, TEL. Cancer Res 1995;55:34–8. [12] Cazzaniga G, Tosi S, Aloisi A, Giudici G, Daniotti M, Pioltelli P, et al. The tyrosine kinase abl-related gene ARG is fused to ETV6 in an AML-M4Eo patient with a t(1;12)(q25;p13): molecular cloning of both reciprocal transcripts. Blood 1999;94:4370–3. [13] Iijima Y, Ito T, Oikawa T, Eguchi M, Eguchi-Ishimae M, Kamada N, et al. A new ETV6/TEL partner gene, ARG (ABLrelated gene or ABL2), identified in an AML-M3 cell line with a t(1;12)(q25;p13) translocation. Blood 2000;95:2126–31. [14] Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, et al. A TEL–JAK2 fusion protein with constitutive kinase activity in human leukaemia. Science 1997;278:1309–12. [15] Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, et al. Fusion of TEL, the ETS-variant gene 6 (ETV6), to the receptor-associated kinase JAK2 as a result of t(9;12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997;90:2535–40. [16] Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH. A novel ETV6–NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet 1998;18:184–7. [17] Yagasaki F, Wakao D, Yokoyama Y, Uchida Y, Murohashi I, Kayano H, et al. Fusion of ETV6 to fibroblast growth factor receptor 3 in peripheral T-cell lymphoma with a t(4;12)(p16;p13) chromosomal translocation. Cancer Res 2001;61:8371–4. [18] Kuno Y, Abe A, Emi N, Iida M, Yokozawa T, Towatari M, et al. Constitutive kinase activation of the TEL–Syk fusion gene in myelodysplastic syndrome with t(9;12)(q22;p12). Blood 2001;97:1050–5. [39] Shurtleff SA, Buijs A, Behm FG, Rubnitz JE, Raimondi SC, Hancock ML, et al. Tel/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 1995;9:1985–9. |
The source is not mentioned here. Note that the table in the source has two more columns which have not been reproduced here in order to improve readability. Note that there are two publicationen "Peeters et. al., 1997" in the bibliography. Note that also Fontanari Krause (2006) (p.22: 13ff) could have been the source of this text. In fact, this source is even closer to the text in the thesis, see Vpr/Fragment 022 01 |
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