In the previous reports we demonstrated overexpression of the dominant-negative isoform of the transcription factor Ikaros, Ik-6, in patients with blast crisis of chronic myelogenous leukemia and B cell acute lymphoblastic leukemia. We extended our analysis and analyzed expression of Ikaros gene family, Ikaros, Aiolos, and Helios, in normal volunteers and patients with hématologie malignancies. Surprisingly we found overexpression of dominant-negative isoforms of Helios in adult T cell leukemia/lymphoma ( ATLL) patients. The HTLV-I virus has a prolonged latency period of decades before clinical syndromes appear. Initially, the T cell proliferation is polyclonal, however in 1 to 5% of infected people an oligoclonal or monoclonal T cell proliferation emerges resulting in the clinical manifestations of ATLL. Chronic and/or smoldering ATLL may evolve into an acute form after many years of indolent disease. We examined 20 ATLL patients (16 acute, one lymphoma, two chronic, and one smoldering), and 6 of them (5 acute and one chronic) overexpressed dominant-negative isoforms of Helios. Not only patients with acute ATLL, but also one patient with chronic ATLL showed overexpression of dominant-negative isoforms of Helios, suggesting decreased Helios activity already in patients with chronic ATLL. We could not detect any overexpression of dominant-negative isoforms of Helios in normal volunteers and healthy carriers of HTLV-I examined so far. Although we could not detect any differences in the restriction fragments with genomic DNA from normal volunteers and patients with dominant-negative isoforms of Helios by Souhtern blotting, these results suggest that Helios may be critical in the development of monoclonal T cell proliferation in HTLV-I infection.
|Issue number||11 PART II|
|Publication status||Published - 2000|
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