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Leuk Res. 2009 Feb;33(2):276-87. doi: 10.1016/j.leukres.2008.06.029. Epub 2008 Aug 8.

Ligand-induced Flt3-downregulation modulates cell death associated proteins and enhances chemosensitivity to idarubicin in THP-1 acute myeloid leukemia cells.

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Proteomic Unit at University of Bergen, Bergen, Norway.


Sustained ligand stimulation of the receptor tyrosine kinase Flt3 resulted in its downregulation and a refractory signaling phase in primary acute myeloid leukemia (AML) cells and in the AML cell line THP-1. Stable isotope amino acid labeling in cell culture and mass spectrometry were used to compare protein expression patterns in THP-1 before and after Flt3-downregulation. 375 distinct proteins were identified where ATP-dependent RNA helicase DDX3, HNRPU, Matrin-3, Importin-7 and Bax were among the 25 most upregulated proteins and Hausp/UBP7, UBE2N and ERp29 among the 17 most downregulated. THP-1 cells with receptor downregulation were sensitized to idarubicin-induced apoptosis but not cytarabine. We hypothesize that FL-induced receptor modulation may chemosensitize selected AML subsets.

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