Expression of growth-regulated genes in human acute leukemias

We have investigated the expression of six growth-regulated genes (c-myc, c-myb, p53, 4F1, 2F1, and ornithine decarboxylase) and the S-phase-specific histone H3 gene in acute myeloid and lymphoid leukemic cells. We have purposely chosen three growth-regulated protooncogenes that share similar biological features and three gene sequences that have in common the cell cycle dependence of their expression in cells of different tissue and in different species. The level of expression was determined by measuring the amounts of specific RNA by Northern blot analysis. Levels of expression of the six growth-regulated genes were compared to the level of expression of the S-phase-specific H3 gene and among themselves. This method distinguishes the increased expression of a growth-regulated gene due to a true altered activation from over-expression which simply reflects an increase in the fraction of cycling cells. We have found that six of 14 patients with acute leukemias have markedly high ratios of c-myc/H3, c-myc/p53, and c-myc/c-myb expression. Two patients with altered c-myc expression have also a high ratio p53/H3. Within the group of cell cycle-dependent genes the ratios of expression seem in the overall much more regular with the clear exception of a patient with acute myelogenous leukemia in which the ratios 4F1/H3 and 2F1/H3 are significantly increased. A possible interpretation of these findings is that the fraction of noncycling leukemic cells that often constitute the majority of the entire leukemic population is in some cases in a true resting state, whereas in other cases heterogeneous degrees of growth arrest might occur. The altered expression of c-myc seems the feature most commonly associated with this putative growth arrest of leukemic cells suggesting that this gene may contribute to the impairment of proliferative control that is associated with the leukemic phenotype.