Differential nucleolar organizer activity in normal and leukemic bone marrow: Its use as a clinical diagnostic tool
Silver nitrate can be used to stain a specific protein associated with the transcriptional activity of ribosomal genes located in the nucleolar organizing regions (NORs) of chromosomes. Using this technique we have studied the activity of NORs in both normal and malignant hematopoietic tissues. This work was begun by establishing levels of NOR activity for normal bone marrow and thymus cells using the AKR mouse as a model. Tumor cells originating from these two tissue types were then studied and significant differences could be determined between the normal and malignant tissues. In order to determine whether these differences in silver staining patterns could be useful clinically, I next studied the number of active NORs in bone marrow cells from 22 patients with acute lymphocytic leukemia (ALL), 11 patients with chronic myelogenous leukemia (CML) and 7 with acute myelogenous leukemia (AML). Bone marrow samples from 16 healthy individuals served as controls. The average number of Ag-NORs increased in patients in accelerated phases and highest in blastic phase. The silver staining pattern for AML was different from ALL with an average number of Ag-NORs per metaphase of 1.19. These disease related differences in NOR activity as detected by silver staining should prove to be useful for clinical diagnostic purposes. Since it is not always possible to obtain sufficient numbers of metaphase spreads from every leukemic bone marrow sample, we have used computer-assisted image analysis to quantitate the amount of silver staining in interphase nuclei of bone marrow cells of acute lymphocytic leukemia patients. By comparing the data obtained for the interphase nuclei with that obtained from the metaphase spreads, we demonstrated a strong correlation between the fraction of bone marrow metaphases stained positively with silver, the average number of Ag-NORs per metaphase, and the amount of silver staining in the interphase nuclei. The results of this study indicate that computer-assisted image analysis of silver stained interphase nuclei can be used to aid in diagnosis and determination of disease status of leukemic patients as well as for evaluation of bone marrow for transplantation, predicting relapse and monitoring the efficacy of treatment. (Abstract shortened with permission of author.)
Arden, Karen Clare, "Differential nucleolar organizer activity in normal and leukemic bone marrow: Its use as a clinical diagnostic tool" (1987). Texas Medical Center Dissertations (via ProQuest). AAI8802903.