Human T-cell leukemia virus type I (HTLV-I) infection and the onset of adult T-cell leukemia (ATL)

Abstract

The clinical entity of adult T-cell leukemia (ATL) was established around 1977, and human T-cell leukemia virus type 1 (HTLV-I) was subsequently identified in 1980. In the 25 years since the discovery of HTLV-I, HTLV-I infection and its associated diseases have been extensively studied, and many of their aspects have been clarified. However, the detailed mechanism of leukemogenesis remains unsolved yet, and the prognosis of ATL patients still poor because of its resistance to chemotherapy and immunodeficiency. In this review, I highlight the recent progress and remaining enigmas in HTLV-I infection and its associated diseases, especially ATL.

Figure 1

Typical "flower cell" in the peripheral blood of an acute ATL patient. In the peripheral blood of an acute ATL patient, leukemic cells with multilobulated nuclei.

Figure 2

Natural course of HTLV-I infection to onset of ATL. HTLV-I is transmitted via three routes, and infected cells are necessary in all three. After infection, HTLV-I promotes clonal proliferation of infected cells by pleiotropic actions of Tax. Tax expression is suppressed by viral accessory gene products, such as Rex, p30 and HBZ proteins. Proliferation of HTLV-I infected cells is controlled by cytotoxic T-cells in vivo. After a long latent period, ATL develops in about 5% of asymptomatic carriers. The expression of Tax is inactivated by several mechanisms, suggesting that Tax is not necessary in this stage. Alternatively, alternations in the host genome accumulate during the latent period, finally leading to onset of ATL.

Figure 3

Increased number of osteoclasts in the bone of a hypercalcemic ATL patient. In a hypercalcemic patient, the number of osteoclast (arrows) increased in the bone, which accelerated bone resorption.