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Phosphoproteomic analysis identifies the M0-91 cell line as a cellular model for the study of TEL-TRKC fusion-associated leukemia

Leukemia volume 21, pages 563–566 (2007)Cite this article

The TEL-TRKC gene fusion associated with the t(12;15)(p13;q25) translocation has been implicated in both hematological (acute myeloid leukemia (AML))1 and non-hematological malignancies (congenital fibrosarcoma, congenital mesoblastic nephroma and secretory breast carcinoma). In AML, the TEL-TRKC (TEL-TRKC(L)) derives from the in-frame fusion of exons 1–4 of TEL to exons 13–18 of TRKC. In contrast, the TEL-TRKC variant associated with solid tumors (TEL-TRKC(F)) contains exons 1–5 of the TEL gene. Activation of both the RAS-MAPK and PI3K-AKT pathways by TEL-TRKC contributes to oncogenic signaling in transfected NIH3T3 cells.2 However, no human cell lines are available to study the TEL-TRKC fusion.

In conclusion, we identified M0-91 as the first cell line expressing the TEL-TRKC fusion gene from its endogenous promoter, and therefore the first valuable cell culture model for the screening for TRKC inhibitors and for understanding both hematological and non-hematological diseases associated with TEL-TRKC. In addition, our phosphoproteomic analysis provided the most comprehensive tyrosine phosphorylation signaling profile reported for TEL-TRKC fusion to date. This information will be useful to develop novel therapeutic approaches for the effective treatment of human cancers associated with deregulated TRKC activity.

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References

  1. Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y et al. Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Blood 1999; 93: 1355–1363.

    CAS  PubMed  Google Scholar 

  2. Tognon C, Garnett M, Kenward E, Kay R, Morrison K, Sorensen PH . The chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation. Cancer Res 2001; 61: 8909–8916.

    CAS  PubMed  Google Scholar 

  3. Okabe M, Kunieda Y, Shoji M, Nakane S, Kurosawa M, Tanaka J et al. Megakaryocytic differentiation of a leukemic cell line, MC3, by phorbol ester: induction of glycoprotein IIb/IIIa and effects on expression of IL-6, IL-6 receptor, mpl and GATA genes. Leuk Res 1995; 19: 933–943.

    Article  CAS  PubMed  Google Scholar 

  4. Rush J, Moritz A, Lee KA, Guo A, Goss VL, Spek EJ et al. Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nat Biotechnol 2005; 23: 94–101.

    Article  CAS  PubMed  Google Scholar 

  5. Walters DK, Mercher T, Gu TL, O’Hare T, Tyner JW, Loriaux M et al. Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 2006; 10: 65–75.

    Article  CAS  PubMed  Google Scholar 

  6. Lamballe F, Tapley P, Barbacid M . TrkC encodes multiple neurotrophin-3 receptors with distinct biological properties and substrate specificities. EMBO J 1993; 12: 3083–3094.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Tsoulfas P, Stephens RM, Kaplan DR, Parada LF . TrkC isoforms with inserts in the kinase domain show impaired signaling responses. J Biol Chem 1996; 271: 5691–5697.

    Article  CAS  PubMed  Google Scholar 

  8. Liu Q, Schwaller J, Kutok J, Cain D, Aster JC, Williams IR et al. Signal transduction and transforming properties of the TEL-TRKC fusions associated with t(12;15)(p13;q25) in congenital fibrosarcoma and acute myelogenous leukemia. EMBO J 2000; 19: 1827–1838.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Cell Signaling Technology, Inc., Danvers, MA, USA

    T-L Gu, L Popova, C Reeves, J Nardone, J MacNeill, J Rush & R D Polakiewicz

  2. Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    S D Nimer

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  1. T-L Gu
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  2. L Popova
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  3. C Reeves
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  6. J Rush
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  8. R D Polakiewicz
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Correspondence to R D Polakiewicz.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Gu, TL., Popova, L., Reeves, C. et al. Phosphoproteomic analysis identifies the M0-91 cell line as a cellular model for the study of TEL-TRKC fusion-associated leukemia. Leukemia 21, 563–566 (2007). https://doi.org/10.1038/sj.leu.2404555

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