Relationship between morphometric analysis of nucleolar organizer regions and cell proliferation in acute leukemias

Silver-stained nucleolar organizer regions in interphase cells have been widely studied as a cell kinetic parameter in different tissues. Many different approaches have been used for this evaluation, often leading to conflicting results. The aim of our study was to analyze several commonly used AgNOR parameters in bone marrow smears of 32 newly diagnosed cases of acute leukemia: number of clusters and dots, percentage of cells with one cluster (cells in a long G1 phase), total and percentage of silver-stained area per nucleus, mean size of AgNORs, and the Rüschoff index. These parameters were compared with the in vitro incorporation of bromodeoxyuridine (BrdU). A significant correlation was found between the BrdU index and the mean number of clusters (r = 0.60), dots (r = 0.60), percentage of cells with one cluster (r = -0.63), as well as with the mean size of AgNORs (r = -0.63) and the Rüschoff index (r = 0.72). In a factor analysis, total AgNOR area, its percentage of nuclear area, the mean AgNOR size, and the nuclear area formed one factor (factor of area parameters), and clusters, dots, the percentage of cells with one cluster, and BrdU index made another factor (factor of proliferation parameters). The Rüschoff index participated equally in both factors. Based on these data, we postulate that the number of clusters and dots are related to the percentage of cells in S-phase and the AgNOR area may be related to the cell duplication time, as has been reported in the literature. Mean size of AgNORs is smaller in highly proliferating cells. Probably the Rüschoff index is related to the percentage of cells in S-phase as well as to the cell duplication time, and seems to be the best AgNOR parameter for the global evaluation of cell kinetics in acute leukemias.