Autonomous and Interleukin-2-Responsive Growth of Leukemic Cells in Adult T-cell Leukemia (ATL): A Review of the Clinical Significance and Molecular Basis of ATL Cell Growth

Abstract

Since the initial report of adult T-cell leukemia (ATL) in 1976, a number of investigators have described the basic biologic aspects of this disease. However, the precise mechanism of leuke-mogenesis remains unclear. Primary ATL cells demonstrate autonomous and IL-2 responsive growth in vitro. The autonomous growth of the cells is thought to be mediated by IL-2 in an autocrine manner, at least in part. These growth activities are related inversely to survival, and may be useful prognostic determinants. The viral Tax protein stimulates IL-2 and IL-2 receptor a expression via nuclear transfer factor NF-kB induction. We showed that marked activation of the Tax-NF-kB pathway is seen only in acute-type ATL patients. Recent studies show that mutations of p16 and p53 are also found in acute and lymphoma-type ATL. These appear to be late events in ATL leukemogenesis. The relationship between activation of Tax-NF-KB 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 and chronic-type ATL. These gene mutations may be accumulated by Tax protein during the long process from the time of HTLV-I infection to the onset of ATL.

Key Words:

• Autonomous growth
• IL-2 responsive growth
• ATL
• adult T cell leukemia