AUTONOMOUS AND INTERLEUKIN 2-RESPONSIVE GROWTH OF LEUKEMIC-CELLS IN ADULT T-CELL LEUKEMIA (ATL) - A REVIEW OF THE CLINICAL-SIGNIFICANCE ANDMOLECULAR-BASIS OF ATL CELL-GROWTH

Since the initial report of adult T-cell leukemia (ATL) in 1976, a num ber of investigators have described the basic biologic aspects of this disease. However, the precise mechanism of leukemogenesis remains unc lear. Primary ATL cells demonstrate autonomous and IL-2 responsive gro wth in vitro. The autonomous growth of the cells is thought to be medi ated by IL-2 in an autocrine manner, at least in part. These growth ac tivities are related inversely to survival, and may be useful prognost ic determinants. The viral Tax protein stimulates IL-2 and IL-2 recept or a expression via nuclear transfer factor NF-kappa B induction. We s howed that marked activation of the Tax-NF-kappa B pathway is seen onl y in acute-type ATL patients. Recent studies show that mutations of p1 6 and p53 are also found in acute and lymphoma-type ATL. These appear to be late events in ATL leukemogenesis. The relationship between acti vation of Tax-NF-kappa B pathway and mutations of p53 and p16 genes is unknown. A few other genetic events may be involved in earlier stages of the entire process of ATL leukemogenesis, leading to smoldering an d chronic-type ATI,. These gene mutations may be accumulated by Tax pr otein during the long process from the time of HTLV-I infection to the onset of ATL.