TEL-JAK2
The TEL-JAK2 gene fusion results from a t(9;12) chromosomal translocation detected in cases of human leukemia.[1][2] The TEL gene (also called ETV6) encodes a transcription factor of the ETS family. The TEL protein contains an oligomerisation domain, and its presence in the TEL-JAK2 protein leads to JAK2 juxtaposition and constitutive activation.
The strong transforming potential of constitutively active TEL-JAK2 has been demonstrated by in vitro and in vivo approaches:
- TEL-JAK2 expression, or any other TEL-JAK fusion, renders the Ba/F3 pro-B cell line interleukin-3-independentb[3];
- bone marrow cells retrovirally transduced with TEL-JAK2 originate a lympho/myeloproliferative disorder after transplantation into irradiated mice[4][5];
- and TEL-JAK2 transgenic expression in lymphoid cells results in the development of highly penetrant clonal or oligoclonal T-cell leukemia/lymphoma in mice.[6]
References
1 ^a Lacronique V, Boureux A, Valle VD, Poirel H, Quang CT, Mauchauffe M, Berthou C, Lessard M, Berger R, Ghysdael J, Bernard OA (1997). "A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia". Science. 278 (5341): 1309–12. PMID 9360930.{{cite journal}}: CS1 maint: multiple names: authors list (link)
2 ^ Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P, Monpoux F, Van Rompaey L, Baens M, Van den Berghe H, Marynen P (1997). "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 (7): 2535–40. PMID 9326218.{{cite journal}}: CS1 maint: multiple names: authors list (link)
3 ^ Schwaller J, Frantsve J, Aster J, Williams IR, Tomasson MH, Ross TS, Peeters P, Van Rompaey L, Van Etten RA, Ilaria R Jr, Marynen P, Gilliland DG (1998). "Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes". EMBO J. 17 (18): 5321–33. PMID 9736611.{{cite journal}}: CS1 maint: multiple names: authors list (link)
4 ^ Lacronique V, Boureux A, Monni R, Dumon S, Mauchauffe M, Mayeux P, Gouilleux F, Berger R, Gisselbrecht S, Ghysdael J, Bernard OA (2000). "Transforming properties of chimeric TEL-JAK proteins in Ba/F3 cells". Blood. 95 (6): 2076–83. PMID 10706877.{{cite journal}}: CS1 maint: multiple names: authors list (link)
5 ^ Carron C, Cormier F, Janin A, Lacronique V, Giovannini M, Daniel MT, Bernard O, Ghysdael J (2000). "TEL-JAK2 transgenic mice develop T-cell leukemia". Blood. 95 (12): 3891–9. PMID 10845925.{{cite journal}}: CS1 maint: multiple names: authors list (link)