title: Expression of the normal p53 gene induces differentiation of K562 cells.
abstract: The multistep nature of human cancers is well illustrated by chronic myelogenous leukemia (CML), a clonal hematologic malignancy with two distinct phases: chronic and acute. Transition between these phases is characterized by unregulated growth and loss of differentiation of myeloid cells and their progenitors. We recently reported that loss of normal p53 expression correlates with transition from the chronic to acute phase in at least 25% of cases of CML. However, the precise relationship between this loss and biologic features of acute-phase CML is uncertain. To study this question, we artificially expressed normal p53 in K562, an erythroid acute-phase CML cell line lacking normal p53 expression. Biological effects were assessed by determining several growth parameters and by measuring synthesis of hemoglobin, a feature of mature erythroid cells. K562 cells expressing normal p53 had an increased proportion of cells in G1 versus S + G2, a longer doubling time and a lower growth saturation density than control K562 cells or K562 cells with antisense p53. Cells with normal p53 also expressed up to 50-fold more hemoglobin than controls. These data are consistent with the notion that loss of p53 expression may be responsible for many of the features of acute-phase CML cells. The data also demonstrate direct involvement of p53 in differentiation processes.
authors.affiliation: Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Feinstein
authors.forename: R P
authors.initials: RP
authors.lastname: Gale
authors.forename: J
authors.initials: J
authors.lastname: Reed
authors.forename: E
authors.initials: E
authors.lastname: Canaani
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D015870:Gene Expression; D016158:Genes, p53; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D006427:Hemin