Adult T-Cell Leukemia-Lymphoma
Summary of Key Points
Virology and Pathogenesis
• HTLV-I is reverse-transcribed into DNA and randomly integrated into the host cell.
• The HTLV-I genome encodes two unique regulatory proteins—Tax and Rex—responsible for viral expression and cellular transformation. Tax trans-activates viral and cellular genes that could be involved in the pathogenesis of ATL. HTLV-I basic leucine zipper (HTLV-I bZIP; HBZ) is an antisense transcript of HTLV-I, is steadily expressed in ATL cells, and interacts with several host genes and suppresses the activity of Tax.
Epidemiology
• A major cluster of HTLV-I–infected individuals and patients with ATL exists on the southwest coast of Japan, where approximately 1.1 million people are infected with the virus.
• Other clusters have been noted in the Caribbean islands (African), tropical Africa (African), South America (Mongoloid), and northern Oceania (Melanesian).
• HTLV-I is transmitted from mother to child through breast-feeding, by sexual contact, and by blood-borne transmission.
• The estimated cumulative risk of the development of ATL in HTLV-I–positive individuals is about 3% after transmission from their mothers.
Clinical Manifestations
• Patients with ATL show diverse clinical features, and four clinical subtypes have been recognized: acute, lymphoma, chronic, and smoldering.
• The typical manifestations of acute-type ATL include circulating neoplastic cells in the peripheral blood, generalized lymph node swelling, hepatosplenomegaly, skin involvement, opportunistic infections, and hypercalcemia.
