title: Childhood leukemias and other hematopoietic malignancies: interdependence between an infectious event and chromosomal modifications.
abstract: A large number of epidemiological observations suggest an infectious origin of hematopoietic malignancies, including various forms of leukemia, nonHodgkin's lymphomas, Hodgkin's lymphomas and multiple myelomas. Incidence of nonHodgkin's lymphomas and Hodgkin's lymphomas, although not of leukemias, is substantially increased under immunosuppression. Specific chromosomal modifications (translocations) resulting in fusion genes frequently emerge as early, but not sufficient, events for malignant progression in most of these conditions. Presently less than 10% of the global incidence of leukemias and lymphomas can be linked to infections (Epstein-Barr virus, human T-lymphotropic retrovirus, human herpesvirus type 8 and Helicobacter pylori). For individual tumor types of the remaining more than 90%, several risk factors have been identified. They include occupational hazards, such as engagement in community services and agriculture, as well as time-space clustering. In childhood leukemias, a protective effect was noted for multiple infections during the first year of life and for at least 6 months of breastfeeding. A high socioeconomic state and absence of multiple contacts during the early phase of life have been described as risk factors. A hypothesis is presented here which combines these observations. It postulates a wide-spread viral infection, nontumorigenic when replication competent, but potentially leukemiogenic or carcinogenic when replication-incompetent viral genomes infect cells with specific chromosomal modifications. Existing data on polyoma-like virus types seem to render members of this or structurally related virus families as putative candidates for these malignancies.
authors.affiliation: Deutsches Krebsforschungszentrum, Angewandte Tumorvirologie, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. zurhausen@dkfz-heidelberg.de
authors.forename: Harald
authors.initials: H
authors.lastname: zur Hausen