In vitro colony forming cells and colony stimulating factor in chronic granulocytic leukaemia

We have used the technique of human haemopoietic cell culture in agar to study the peripheral blood and bone marrow colony forming capacity of 23 patients with Ph(1) + ve chronic granulocytic leukaemia (CGL) before and after treatment. In comparison with normal controls the number of colony forming cells (CFC) is moderately increased (about three-fold) in the bone marrow and enormously increased in the peripheral blood of untreated patients. In the peripheral blood their number in general is related to the total leucocyte count. In patients whose blood counts have been restored to normal by the use of cytotoxic drugs the number of CFC in the peripheral blood is very greatly reduced. In the marrow of treated patients CFC are present in approximately normal numbers. When used as feeder layer sto support the culture of normal bone marrow cells, the peripheral blood leucocytes of untreated patients are a uniformly poor source of colony stimulating factor (CSF) and fractionation experiments suggest that this is not due merely to a relative scarcity of monocytes. After treatment the peripheral blood has normal CSF activity and this is associated with the monocytic cell component. The last data may be explained in either of two ways: it is possible that restoration of the blood of patients with CGL to normal values removes a homeostatic factor suppressing the formation of CSF by functionally normal monocytes, or alternatively treatment with cytotoxic drugs leads to the replacement of defective monocytes by a population of relatively normal CSF producing cells.