Molecular and cellular aspects of HTLV-1 associated leukemogenesis in vivo

Most cancers and leukemias are preceded by a prolonged period of clinical latency during which cellular, chromosomal and molecular aberrations help move normal cell towards the malignant phenotype. The problem is that premalignant cells are usually indistinguishable from their normal counterparts, thereby ruling out the possibility to investigate the events that govern early leukemogenesis in vivo. Adult T cell leukemia/lymphoma (ATLL) is a T cell malignancy that occurs after a 40-60-year period of clinical latency in about 3-5% of HTLV-1-infected individuals. ATLL cells are monoclonally expanded and harbor an integrated provirus. A persistent oligo/polyclonal expansion of HTLV-1-bearing cells has been shown to precede ATLL, supporting the fact that in ATLL tumor cells arise from a clonally expanding non-malignant cell. It is possible to isolate infected, ie preleukemic, cells during the premalignant asymptomatic phase of the infection, thus providing an exceptional system to study the mechanisms underlying human cancers. Here we review some of the consequences of HTLV-1 on its host cell in vivo, at different stages of infection.