Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent for the development of an aggressive hematologic neoplasia termed adult T cell leukemia/lymphoma (ATLL). Although the virus infects T cell subsets that display either CD4 or CD8 cell surface markers, the leukemic cell is exclusively of the CD4+ subtype. In the article by Sibon et al. in this issue of the JCI, the authors demonstrate that the molecular basis for clonal expansion differs between these 2 infected T cell populations (see the related article beginning on page 974). The molecular events associated with a preleukemic state, such as genomic instability, polynucleation, and cell cycle redistribution, were only observed in CD4+ T cells. This finding provides a molecular-based mechanism for the restriction of the leukemic phenotype to the CD4+ T cell subtype.