In vivo 5-Aza therapy reveres silenced TSC-22 gene expression and prolongs survival in mice bearing T or NK LGL leukemia. (A) In vivo treatment of mice moribund with T or NK LGL leukemia using PBS (“untreated,” ▵) or 5-Aza (▴) for 4 consecutive days shows a significant reversal, with up-regulation of TSC-22 expression as assessed by real-time RT-PCR (P < .05). Horizontal bars indicate mean values. The TSC-22 expression levels of the untreated samples were normalized to 1. (B) One million primary T or NK LGL leukemia cells from IL-15tg mice were adoptively transferred into sublethally irradiated WT FvB mouse recipients. When engrafted mice showed progressive disease, they received daily subcutaneous injections with either 1 or 2 cycles of the indicated dose of 5-Aza or PBS for 4 consecutive days. Mice receiving 2 cycles of therapy had 4 days of rest between cycles at doses of 12 μg or 8 days of rest between cycles at doses of 32 μg. As shown by the Kaplan-Meier curve, mice given increasing doses and/or cycles of 5-Aza displayed prolonged survival compared with control mice treated with PBS (P < .001 among all groups).