Acute lymphoblastic leukemia

Leukemic cells expressing NCOR1-LYN are sensitive to dasatinib in vivo in a patient-derived xenograft mouse model

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Fig. 1: Cell proliferation and gene expression of Ba/F3 cells induced by NCOR1-LYN.
Fig. 2: Effects of dasatinib and rapamycin on NCOR1-LYN.

References

  1. 1.

    Roberts KG. Why and how to treat Ph-like ALL? Best Pr Res Clin Haematol. 2018;31(4):351–6.

    Article  Google Scholar 

  2. 2.

    Yano M, Imamura T, Asai D, Kiyokawa N, Nakabayashi K, Matsumoto K, et al. Identification of novel kinase fusion transcripts in paediatric B cell precursor acute lymphoblastic leukaemia with IKZF1 deletion. Br J Haematol. 2015;171(5):813–7.

    CAS  Article  Google Scholar 

  3. 3.

    Reshmi SC, Harvey RC, Roberts KG, Stonerock E, Smith A, Jenkins H, et al. Targetable kinase gene fusions in high-risk B-ALL: a study from the Children’s Oncology Group. Blood. 2017;129(25):3352–61.

    CAS  Article  Google Scholar 

  4. 4.

    Tanaka H, Takeuchi M, Takeda Y, Sakai S, Abe D, Ohwada C, et al. Identification of a novel TEL-Lyn fusion gene in primary myelofibrosis. Leukemia. 2010;24(Jan):197–200.

    CAS  Article  Google Scholar 

  5. 5.

    Dai H-P, Yin J, Li Z, Yang C-X, Cao T, Chen P, et al. Rapid molecular response to dasatinib in a pediatric relapsed acute lymphoblastic leukemia with NCOR1-LYN Fusion. Front. Oncol. 2020;10:359.

  6. 6.

    Piet Borst RE, Kool Marcel, Wijnholds Jan. A family of drug transporters: the multidrug resistence-associated proteins. J Natl Cancer Inst. 2000;92(16):1295–302.

    Article  Google Scholar 

  7. 7.

    Guo Y, Shan Q, Gong Y, Lin J, Yang X, Zhou R. Oridonin in combination with imatinib exerts synergetic anti-leukemia effect in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway. Cancer Biol Ther. 2012;13(13):1244–54.

    CAS  Article  Google Scholar 

  8. 8.

    Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 2004;18:1926–45.

    CAS  Article  Google Scholar 

  9. 9.

    Yang K, Fu LW. Mechanisms of resistance to BCR-ABL TKIs and the therapeutic strategies: a review. Crit Rev Oncol Hematol. 2015;93(3):277–92.

    Article  Google Scholar 

  10. 10.

    Patel AB, O’Hare T, Deininger MW. Mechanisms of resistance to ABL kinase inhibition in chronic myeloid leukemia and the development of next generation ABL kinase inhibitors. Hematol Oncol Clin North Am. 2017;31(4):589–612.

    Article  Google Scholar 

  11. 11.

    Gotesman M, Vo TT, Herzog LO, Tea T, Mallya S, Tasian SK. et al. mTOR inhibition enhances efficacy of dasatinib in ABL-rearranged Ph-like ALL. Oncotarget. 2018;9(5):6562–71.

    Article  Google Scholar 

  12. 12.

    Tasian SK, Teachey DT, Li Y, Shen F, Harvey RC, Chen IM, et al. Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood. 2017;129(2):177–87.

    CAS  Article  Google Scholar 

  13. 13.

    Feldhahn N, Arutyunyan A, Stoddart S, Zhang B, Schmidhuber S, Yi SJ, et al. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia. Oncoimmunology. 2012;1(6):618–29.

    Article  Google Scholar 

  14. 14.

    Delgado MD, Leon J. Myc roles in hematopoiesis and leukemia. Genes Cancer. 2010;1(Jun):605–16.

    CAS  Article  Google Scholar 

  15. 15.

    Faber J, Krivtsov AV, Stubbs MC, Wright R, Davis TN, van den Heuvel-Eibrink M, et al. HOXA9 is required for survival in human MLL-rearranged acute leukemias. Blood. 2009;113(11):2375–85.

    CAS  Article  Google Scholar 

Download references

Acknowledgements

This study was supported by grants-in-aid for scientific research from the Japanese Ministry of Education, Culture, Sports, Science and Technology (17K10124 and 17K16277) and by Grant-in-Aid for Practical Research for Innovative Cancer Control (16ck0106066h0003, 17ck0106253h0001, 18ck0106253h0002, and 19ck0106253h0003).

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T.T. and T.I. designed studies and wrote the manuscript; T.T., T.I., A.M., E.S., M.Y., K.S., and N.K. performed genetic and in vitro functional studies; K.T., I.K., T.M., and M.M. performed in vivo studies using patient-derived xenograft model; K.H., S.A., T.N., J.T., and H.H. supervised research and participated in editing manuscript.

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Correspondence to Toshihiko Imamura.

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Tomii, T., Imamura, T., Tanaka, K. et al. Leukemic cells expressing NCOR1-LYN are sensitive to dasatinib in vivo in a patient-derived xenograft mouse model. Leukemia (2020). https://doi.org/10.1038/s41375-020-01091-3

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