HTLV-1 hijacks T-cell differentiation/function by deregulatingHelios gene expression

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Adult T-cell leukemia is a T-cell neoplasm caused by HTLV-1 infection. In the present study, we found drastic deregulation of Helios expression in ATL cells. Helios is an Ikaros-family transcription factor and a pivotal regulator of T-cell differentiation and activation. Detailed investigations in transcript variants of Helios in PBMCs from ATL patients clarified that the majority of ATL patients demonstrated abnormal splicing patterns of Helios mRNAs, while four cases did not express Helios mRNA at the detectable level. We identified ATL-specific short Helios transcripts and further confirmed that resultant isoforms not only functioned dominant-negatively, but also reduced apoptotic sensitivity and increased proliferation of the cells, probably through activation of S1P pathway, which is deeplyimplicated to cell-motility and proliferation.