Altered expression of Tfg and Dap3 in Ikaros-defective T-cell lymphomas induced by X-irradiation in B6C3F1 mice.

Ikaros is a Kruppel-type zinc finger protein that is essential for normal lymphocyte development and differentiation. Recently, it has been demonstrated that Ikaros is frequently inactivated in both human and mouse leukaemias/lymphomas. Although this inactivation is thought to be involved in leukaemogenesis, little is known about the molecular mechanisms that lead to neoplastic transformation. To identify the genes that may be controlled by Ikaros, we performed differential display analysis of RNAs from mouse 3T3-L1 cells that had been transfected with the Ikaros gene. Two cDNAs, the Trk-fused gene (Tfg) and death-associated protein 3 gene (Dap3) were upregulated in Ikaros-transfected cells. Expression of Tfg and Dap3 was consistently downregulated in radiation-induced T-cell lymphomas that exhibited defective Ikaros expression. These results suggest that Tfg and Dap3 function downstream of Ikaros and may be involved in radiation-induced lymphomagenesis.