The Clinical Pathway of Human T-Lymphotropic Virus Type-1 (HTLV-1) from Infection to Leukemia: A Comprehensive Review

Abstract

Human T-lymphotropic virus type 1 (HTLV-1), a member of the Retroviridae family, is a pathogenic retrovirus that primarily includes two clinically relevant types: HTLV-1 and HTLV-2. HTLV-1 is etiologically linked to adult T-cell leukemia/lymphoma (ATLL), a highly aggressive hematological malignancy. The principal modes of HTLV-1 transmission are mother-to-child (predominantly via breastfeeding), sexual contact, and exposure to contaminated blood products. The viral oncoprotein Tax and HTLV-1 basic leucine zipper factor are central to the virus’s oncogenic potential, orchestrating a cascade of genetic and molecular alterations that drive the clonal proliferation and malignant transformation of infected lymphocytes over a prolonged latent period, often spanning several years. Despite extensive research, the precise mechanisms underlying the clonal evolution and emergence of leukemic cells remain incompletely elucidated. Diagnosis typically relies on a two-step serological screening approach. While preventive strategies have been implemented, HTLV-1, like other retroviruses, persists as a lifelong infection, and no definitive cure or effective vaccine is currently available. This comprehensive review delineates the pathophysiological continuum from HTLV-1 infection to ATLL, emphasizing the molecular underpinnings of viral oncogenesis, the clinical relevance of early leukemia detection, and the current challenges in prevention and management.

Keywords

• Adult T-cell leukemia
• Human T-lymphotropic virus type 1
• Leukemia
• Carcinogenesis

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