EVIDENCE OF COLONY SUPPRESSOR ACTIVITY AND DEFICIENCY OF HEMATOPOIETIC GROWTH-FACTORS IN HAIRY-CELL LEUKEMIA

The cause of myelosuppression in hairy cell leukemia (HCL) has been as cribed to a reduction of the circulating progenitor cell (CPC) compart ment and to suppression of hematopoiesis by TNF-alpha. The present stu dy was performed to evaluate the inhibitory effect of hairy cells (HCs ) and a possible lack of hematopoietic growth factors on the number of autologous CPCs in vitro. In initial experiments the number of circul ating BFU-E, CFU-GM and CFU-mix in HCL patients was found decreased. M onocytopenia but not the number of circulating HCs correlated to the d egree of colony reduction in our patients. This pointed to a lack of c olony stimulating factors (CSFs) in HCL. Actually, the growth of BFU-E , CFU-GM, and CFU-mix improved upon the addition of IL-3 and GM-CSF in HCL patients but not in healthy donors. To test the suppressive role of HCs in our assay system, cultures were performed after removal of a utologous HCs. The results showed that in HC-depleted cultures the num bers of BFU-F, CFU-GM, and CFU-mix were significantly higher. This inh ibitory effect of HCs could partially be neutralized by the addition o f monoclonal antibodies against TNF-alpha. When the assays were perfor med with the removal of HCs and the addition of CSFs normal progenitor cell counts were detected in most patients. We conclude that HCs medi ate the inhibition of colony growth in part by TNF-alpha. Monocytopeni a is related with a deficiency of CSFs in this disease. The reduced co lony growth in HCL, therefore, is due to both the inhibitory effects o f HCs and the deficiency of CSFs. We suppose that the CPC-compartment is actually preserved in this disease.