Dominant negative isoform of the Ikaros gene in patients with adult B-cellacute lymphoblastic leukemia

Gene targeting studies in mice have shown that the transcription factor Ika ros plays an essential role in lymphoid development and as a tumor suppress or in T cells, whereas the related gene Aiolos functions as a tumor suppres sor in B cells. We analyzed the expression levels of the Ikaros gene family , Ikaros and Aiolos, in human bone marrow samples from patients with adult acute lymphoblastic leukemia [ALL (n = 46; B-cell ALL = 41; T-cell ALL = 5) ]. Overexpression of the dominant negative isoform of Ikaros gene Ik-6 was observed in 14 of 41 B-cell ALL patients by reverse transcription-PCR, and the results were confirmed by sequencing analysis and immunoblotting, None of the other dominant negative isoforms of the Ikaros gene were detected by reverse transcription-PCR analysis, Southern blotting analysis with PstI d igestion revealed that those patients with the dominant negative isoform Ik -6 might have small mutations in the Ikaros locus. We did not detect any ov erexpression of dominant negative isoforms of Aiolos in adult ALL patients. These results suggest that Ikaros plays a key role in human B-cell maligna ncies through the dominant negative Isoform Ik-6.