Abstract
Acute myeloid leukemia makes up about 30% of all leukemia cases in adults. Mutations in the genes of the receptor tyrosine kinases KIT and FLT3, along with chromosomal translocations, are frequently found in leukemic cells. In the current work, we show that the transgenic B-cells BAF3/FLT3-ITD are significantly more sensitive to cytotoxic action of the ribonuclease binase than original BAF3 cells. BAF3/FLT3-ITD cells differ from BAF3 in expression of the FLT3-ITD oncogene, which results in the alteration of normal signaling pathways. We observed a similar effect previously when studying binase cytotoxic action in cells Kasumi-1 and FDC-P1-N822K, in which the activated oncogene KIT-N822K was expressed. An elevated cytotoxicity of binase to the cells that express the FLT3-ITD oncogene indicates that, as in case of the FDC-P1 cells transduced by the KIT oncogene, the expression of an activated oncogene determines the cell’s sensitivity to the binase action.
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References
Rulina A.V., Spirin P.V., Prassolov V.S. 2010. Activated leukemic oncogenes AML1-ETO and C-KIT: Role in development of acute myeloid leukemia and current approaches for their inhibition. Biochemistry (Moscow), 75 (13), 1650–1666.
Ilinskaya O.N., Zelenikhin P.V., Petrushanko I.Y., Mitkevich V.A., Prassolov V.S., Makarov A.A. 2007. Binase induces apoptosis of transformed myeloid cells and does not induce T-cell immune response. Biochem. Biophys. Res. Commun. 361, 1000–1005.
Mitkevich V.A., Petrushanko I.Y., Kretova O.V., Spirin P.V., Zelenikhin P.V., Prassolov V.S., Tchurikov N.A., Ilinskaya O.N., Makarov A.A. 2010. Oncogenic c-kit transcript is a target for binase. Cell Cycle. 9, 2674–2678.
Mitkevich V.A., Petrushanko I.Yu, Spirin P.V., Fedorova T.V., Kretova O.V., Tchurikov N.A., Prassolov V.S., Ilinskaya O.N., Makarov A.A. 2011. Sensitivity of acute myeloid leukemia Kasumi-1 cells to binase toxic action depends on the expression of KIT and AML1-ETO oncogenes. Cell Cycle. 10, 4090–4097.
Petrushanko I.Yu., Zelenikhin P.V., Mit’kevich V.A., Kleimenova A.A., Prasolov V.S., Makarov A.A., Il’inskaya O.N. 2007. Binase possesses a selective cytototoxic effect on kit-transformed precursors of myeloid cells. Biofizika (Russian). 52, 876–881.
Masson K., Ronnstrand L. 2009. Oncogenic signaling from hematopoietic growth factors c-Kit and Flt3. Cell Signalling. 21, 1717–1726.
Schulga A., Kurbanov F., Kirpichnikov M., Protasevich I., Lobachev V., Ranjbar B., Chekhov V., Polyakov K., Engelborghs Y., Makarov A. 1998. Comparative study of binase and barnase: Experience in chimeric ribonucleases. Protein Engineering. 11, 775–782.
Karasuyama H., Melchers F. 1988. Establishment of mouse cell lines which constitutively secrete large quantitities of interleukin 2, 3, 4, or 5, using modified cDNA expressing vectors. Eur. J. Immunol. 18, 97–104.
Takahashi S. 2011. Downstream molecular pathways of FLT3 in the pathogenesis of acute myeloid leukemia: Biology and therapeutic implications. J. Hematol. Oncol. 4, 13.
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Original Russian Text © V.A. Mitkevich, N.N. Orlova, I.Yu. Petrushanko, O.V. Simonenko, P.V. Spirin, M.M. Prokof’eva, A.S. Gornostaeva, C. Stocking, A.A. Makarov, V.S. Prassolov, 2013, published in Molekulyarnaya Biologiya, 2013, Vol. 47, No. 2, pp. 282–285.
These authors contributed equally to this work.
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Mitkevich, V.A., Orlova, N.N., Petrushanko, I.Y. et al. Expression of the FLT3-ITD oncogene sensitizes murine progenitor B-cell line BAF3 to cytotoxic action of binase. Mol Biol 47, 248–251 (2013). https://doi.org/10.1134/S002689331302009X
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DOI: https://doi.org/10.1134/S002689331302009X