title: A proposal for the development of clonal hemopoietic leukemias.
abstract: We elaborate on the pathogenesis of (human) hemopoietic leukemias according to a model whereby malignant growth follows the anachronistic expression of gene P in a rare cell at a certain stage of differentiation (1,2). P is a stimulus needed for renewal of hemopoietic cells. When illegally autocatalytic for P any mitotically competent cell (not necessarily pluripotent, at least originally) acquires the marginal (seldom complete) autonomous growth of malignant cells. Rather than confrontational, these views complement advantageously the mutation model and account for certain peculiarities of (human) leukemic cells, such as the propensity to differentiate terminally when isolated from their in vivo microenvironments. In addition, we discuss the rare occurrence of certain human leukemias (e.g., erythroleukemias and polycythemia veras) comparatively to the surprisingly more frequent chronic and acute myelogenous leukemias. This occurs in spite of the similarity between erythroid and myeloid populations in terms of size (mass of cells) and number of targets at mutational risk. Thus the classic mutation model predicts that random hits, after radiation exposure for example, should induce erythroid and myeloid leukemias with similar frequencies in contrast to clinical findings (3) and the predictions from our model.
authors.affiliation: USC Medical School, Los Angeles 90033.
authors.forename: G T
authors.initials: GT
authors.lastname: Matioli
mesh_terms: D002455:Cell Division; D002460:Cell Line; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000235:genetics*; D007951:Leukemia, Myeloid / Q000235:genetics; D008957:Models, Genetic; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000502:physiology; D012307:Risk Factors; D014407:Tumor Cells, Cultured / Q000502:physiology
chemical_list: D004273:DNA, Neoplasm