Vol 47(2013) N 2 p. 248-251;
V.A. Mitkevich1,2, N.N. Orlova2, O.V. Simonenko2, P.V. Spirin2, M.M. Prokofeva2, C. Stocking3, A.A. Makarov2, V.S. Prasolov2*
Expression of the FLT3-ITD Oncogene Sensitizes Murine Progenitor B-Cell Line BAF3 to Cytotoxic Action of Binase1University of Oslo, Centre for Medical Studies in Russia, Moscow, 119334
2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
3Heinrich-Pette Institute Leibniz Institute for Experimental Virology, Hamburg, D-20251, Germany
Received - 2012-09-04; Accepted - 2012-09-17
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.
acute myeloid leukemia, oncogenes, FLT3-ITD, binase, ribonuclease, cytotoxicity