Dynamics of HTLV-1 leukemogenesis: data acquisition for computer modeling.

A literature search for HTLV-1-induced adult T-cell leukemia (ATL) at the National Library of Medicine resulted in 1003 publications which were evaluated with regard to HTLV-1 virus load, apoptosis and peripheral blood leukocyte changes during the latent period and leukemia development following virus infection. The data are presented in a comparable way to previous publications of infections with HHV-6 and HIV (which target the same CD4+ cell for infection) to be used for computer validation studies. After initial infection, HTLV-1 remains clinically latent for many years at low provirus copy numbers in CD4 cells. Once immune surveillance deteriorates and viral replication progresses, provirus copy numbers increase rapidly. Unlike other virus infections, apoptotic death of virus-infected "atypical" lymphocytes decreases with increasing viral load, thus favoring continued proliferation of these cells and further virus replication at the same time. Changes in the peripheral blood are characterized by coincident rises in oligoclonal lymphocyte populations including HTLV-1-positive CD4+ T-lymphocytes and their precursors with a progressive shift to immature cells as disease progresses. The pathogenesis of HTLV-1-induced adult T-cell leukemia is an example of dysregulative leukemogenesis ideal for validation of respective computer simulation models.