The Ikaros gene has been implicated in lymphoid development and proliferation from the results of gene targeting studies in mice. Recently we reported that the Ikaros gene may be involved in the
disease progression of
chronic myelogenous leukemia (CML). In this report, we investigated Ikaros
isoforms in human non-
lymphoid leukemia cell lines and normal granulocyte/macrophage (CFU-GM) and erythroid (BFU-E)-derived colonies. We evaluated Ikaros gene expression by RT-PCR, Southern blotting, sequencing analysis, Northern blotting, and immunoblotting.Ikaros
isoforms Ik-1 and Ik-2, 3 were predominantly expressed in human non-
lymphoid leukemia cell lines. Ik-4 and Ik-8 were also detectable as a minor population. In contrast to the previous report in mice, multiple Ikaros
isoforms were expressed in human CFU-GM and BFU-E-derived colonies, and the dominant-negative
isoform Ik-6 was not detectable. We also showed that human Ikaros
isoforms contained an additional coding sequence in the N-terminal region, which was highly homologous to the sequence reported in mice. These observations suggest that the Ikaros gene may play some role in the development of human non-lymphoid lineage hematopoiesis. Moreover, the finding that the dominant-negative
isoform Ik-6, which was overexpressed in patients with
blast crisis of CML, was rarely detectable in non-lymphoid lineages supports its pathogenetic role in human
hematologic malignancies.