Ligand-independent dimerization of FLT3 fusion proteins

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

In addition to internal tandem duplications and activating point mutations, the FLT3 locus is also subject at low frequency to translocations (reviewed in Reiter and Gotlib, 2017; Kazi and Roonstrand, 2019). These translocations generally bring together an N-terminal partner gene encoding a dimerization domain with the intracellular portion of FLT3 containing the kinase domain and result in a protein that undergoes constitutive, ligand-independent dimerization. To date, 6 fusion partner genes have been identified: ETV6 (the most frequent), GOLGB1, SPTBN1, ZMYM2, TRIP11 and MYO18A, although not all have been functionally characterized. Where examined, the fusion proteins promote downstream signaling through the PI3K/AKT, MAP kinase and STAT5 signaling pathways and support IL-3-independent transformation of murine BaF3 cells (Baldwin et al, 2007; Vu et al, 2006; Vu et al, 2009; Walz et al, 2011; Falchi et al, 2014; Chung et al, 2017; Troadec et al, 2017; Grand et al, 2007; Jawhar et al, 2017; Zhang et al, 2018; Chonabayashi et al, 2013; reviewed in Kazi and Roonstrand, 2019).

Literature References
PubMed ID Title Journal Year
31066629 FMS-like Tyrosine Kinase 3/FLT3: From Basic Science to Clinical Implications

Kazi, JU, Rönnstrand, L

Physiol. Rev. 2019
28751768 Cytogenetically cryptic ZMYM2-FLT3 and DIAPH1-PDGFRB gene fusions in myeloid neoplasms with eosinophilia

Jawhar, M, Naumann, N, Knut, M, Score, J, Ghazzawi, M, Schneider, B, Kreuzer, KA, Hallek, M, Drexler, HG, Chacko, J, Wallis, L, Fabarius, A, Metzgeroth, G, Hofmann, WK, Chase, A, Tapper, W, Reiter, A, Cross, NCP

19345670 The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

Vu, HA, Xinh, PT, Kano, Y, Tokunaga, K, Sato, Y

21705501 Response of ETV6-FLT3-positive myeloid/lymphoid neoplasm with eosinophilia to inhibitors of FMS-like tyrosine kinase 3

Walz, C, Erben, P, Ritter, M, Bloor, A, Metzgeroth, G, Telford, N, Haferlach, C, Haferlach, T, Gesk, S, Score, J, Hofmann, WK, Hochhaus, A, Cross, NC, Reiter, A

30559310 Two myeloid leukemia cases with rare FLT3 fusions

Zhang, H, Paliga, A, Hobbs, E, Moore, S, Olson, S, Long, N, Dao, KT, Tyner, JW

23168613 Direct binding of Grb2 has an important role in the development of myeloproliferative disease induced by ETV6/FLT3

Chonabayashi, K, Hishizawa, M, Kawamata, S, Nagai, Y, Ohno, T, Ishikawa, T, Uchiyama, T, Takaori-Kondo, A

Leukemia 2013
28028030 Myeloid neoplasms with eosinophilia

Reiter, A, Gotlib, J

16761019 FLT3 is fused to ETV6 in a myeloproliferative disorder with hypereosinophilia and a t(12;13)(p13;q12) translocation

Vu, HA, Xinh, PT, Masuda, M, Motoji, T, Toyoda, A, Sakaki, Y, Tokunaga, K, Sato, Y

29025582 A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia

Chung, A, Hou, Y, Ohgami, RS, Von Gehr, A, Fisk, DG, Roskin, KM, Li, X, Gojenola, L, Bangs, CD, Arber, DA, Fire, AZ, Cherry, AM, Zehnder, JL, Gotlib, J, Merker, JD

27795560 A novel t(3;13)(q13;q12) translocation fusing FLT3 with GOLGB1: toward myeloid/lymphoid neoplasms with eosinophilia and rearrangement of FLT3?

Troadec, E, Dobbelstein, S, Bertrand, P, Faumont, N, Trimoreau, F, Touati, M, Chauzeix, J, Petit, B, Bordessoule, D, Feuillard, J, Bastard, C, Gachard, N

17268528 Transgenic mice expressing Tel-FLT3, a constitutively activated form of FLT3, develop myeloproliferative disease

Baldwin, BR, Li, L, Tse, KF, Small, S, Collector, M, Whartenby, KA, Sharkis, SJ, Racke, F, Huso, D, Small, D

17764812 A constitutively active SPTBN1-FLT3 fusion in atypical chronic myeloid leukemia is sensitive to tyrosine kinase inhibitors and immunotherapy

Grand, FH, Iqbal, S, Zhang, L, Russell, NH, Chase, A, Cross, NC

24854988 ETV6-FLT3 fusion gene-positive, eosinophilia-associated myeloproliferative neoplasm successfully treated with sorafenib and allogeneic stem cell transplant

Falchi, L, Mehrotra, M, Newberry, KJ, Lyle, LM, Lu, G, Patel, KP, Luthra, R, Popat, U, Verstovsek, S

Participant Of
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Cite Us!