C. Gasche et al., EVIDENCE OF COLONY SUPPRESSOR ACTIVITY AND DEFICIENCY OF HEMATOPOIETIC GROWTH-FACTORS IN HAIRY-CELL LEUKEMIA, Hematological oncology, 11(2), 1993, pp. 97-104
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.