Granulopoiesis in Chronic Myeloid Leukemia. II. Serial Cloning of Blood and Bone Marrow Cells in Agar Culture

Colony-forming cells (CFC) and CFC in S-phase were assayed in chronic myeloid leukemia (CML). A correlation was found between leukocyte counts and CFC of blood, suggesting that the leukocytosis of CML depended on expansion of the committed granulopoietic stem cell compartment. Serial studies performed in four cases demonstrated a decrease of the CFC in S-phase during early stages of developing leukocytosis, which was consistent with the operation of growth control mechanisms. During later stages, serial studies revealed that sudden increments of CFC S-phase coincided with rapidly growing leukocytosis, which was consistent with leukemic cell populations escaping growth control. 3H-thymidine labeling indices for differentiated precursor cells showed slight variations not coinciding with variations of the CFC S-phase fraction. Cyclic oscillations of the white cell count were observed in one case. The white cell count and the fraction of CFC in S-phase displayed a direct relationship, indicating that the occurence of cycles was not likely to be due to a negative feedback mechanism elaborated by mature granulocytes. In another case, marked cycling of the CFC S-phase fraction was found without distinct oscillations of the white cell count. The present work has emphasized the necessity for serial assays of parameters of cell kinetics in vitro in CML since changing relationships were found between stem cell and differentiated cell kinetics during different phases of the disease.