Cell-cycle-specific genes differentially expressed in human leukemias.

Three cDNA clones isolated from Syrian hamster cells (p4F1, p2F1, and p2A9) contain sequences that are preferentially expressed in the G1 phase of the cell cycle. The expression of these sequences was investigated in human peripheral blood cells from normal individuals and from patients with leukemia. The expression of p4F1 and p2F1 is clearly dependent on the cell cycle in peripheral blood mononuclear cells stimulated to proliferate with phytohemagglutinin; the p2A9 sequences cannot be clearly detected in human lymphocytes but are expressed in a cell-cycle-dependent manner in human diploid fibroblasts (WI-38). These genes also show different levels of expression in lymphoid and myeloid leukemias. The highest level of expression for p2A9 is found in patients with chronic myelogenous leukemia, and the lowest in patients with chronic lymphocytic leukemia. For p2F1 and p4F1, the highest levels of expression are found in chronic and acute myelogenous leukemia. At least two other cell-cycle genes are not expressed at detectable levels in human leukemias. These findings suggest that the activation of cell-division-cycle genes might contribute, like cellular oncogenes, to the phenotype of human malignancies and that, perhaps, new oncogenes could be found by identifying and isolating genes whose expression is dependent on the cell cycle.