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Int J Hematol. 2013 Jan;97(1):83-91. doi: 10.1007/s12185-012-1232-5. Epub 2012 Dec 19.

Fadd and Skp2 are possible downstream targets of RUNX1-EVI1.

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  • 1Department of Hematology and Oncology, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu-machi, Shimotsuga-gun, Tochigi, Japan.


RUNX1-EVI1 generated by t(3;21) is a causative gene in the leukemic transformation of chronic hematopoietic stem cell tumors. Recruitment of histone deacetylase via carboxyl terminal-binding protein by RUNX1-EVI1 results in transcriptional dysregulation in target genes of wild-type RUNX1, leading to differentiation block and apoptotic prevention of myeloid precursor cells. In the present study using mouse primary hematopoietic cells, we confirmed that RUNX1-EVI1 enhances replating activity of hematopoietic colonies and represses differentiation along the myeloid lineage under treatment with granulocyte colony-stimulating factor. We then observed that these biological effects of RUX1-EVI1 are canceled by the treatment of histone deacetylase inhibitors, trichostatin A and valproic acid. To identify target genes whose expression is suppressed by RUNX1-EVI1, we compared the expression profiles of apoptosis and cell-cycle-related genes in control and RUNX1-EVI1-expressing cells, and in RUNX1-EVI1-expressing cells with and without treatment with histone deacetylase inhibitors. Notably, the expression of three genes, Fadd, Skp2 and CD40lg, was found to be suppressed in RUNX1-EVI1-expressing cells and to be recovered on treatment with histone deacetylase inhibitors. Considering that these genes have some RUNX1-binding sites, they may be direct or indirect targets of RUNX1-EVI1, and changes in their expression may play some role in leukemogenesis by RUNX1-EVI1.

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