Myelosuppression in HCL: role of hairy cells, T cells and haematopoietic growth factors.
To elucidate mechanisms which may be responsible for the haematopoietic insufficiency in hairy cell leukaemia (HCL), we investigated in an autologous in vitro system the influence of haematopoietic growth factors (CSFs) and the effects of hairy cells (HCs) as well as T cells on the formation of haematopoietic colonies (CFU). Colony forming assays were performed using peripheral blood mononuclear cells (PBMC) of 6 HCL patients. To remove HCs, PBMCs were subjected to complement-mediated lysis, T cells were removed by E-rosette formation. Assays were done with and without recombinant human (rh) interleukin-3 (IL-3) and rh granulocyte-macrophage-colony-stimulating factor (GM-CSF). All 6 patients exhibited a severe reduction of their circulating progenitor cell (CPC) compartment. There was no correlation between the degree of colony reduction and the number of HCs. However, a correlation was found between the numbers of CPCs of HCL patients and healthy donors and the monocyte counts in these groups (r = 0.8573, p < 0.001). The removal of autologous HCs, but also of T cells, resulted in a significant increase in colony formation (BFU-E, CFU-GM, CFU-mix). In none of the experiments, however, did colony numbers come close to the normal range. This was only achieved by supplementation of the culture medium with rh IL-3 and rh GM-CSF. The results suggest that the haematopoietic failure observed in HCL patients is probably due to an inadequate supply of CSFs as well as to an inhibitory activity of HCs and T cells which might exert their effects in a synergistic fashion. There is also evidence that the lack of monocytes plays a role in the development of the haematopoietic insufficiency in HCL.
Schwarzmeier
J D
JD
Department of Haematology, University of Vienna, Austria.
Gasché
C G
CG
Hilgarth
M F
MF
Reinisch
W W
WW
Göbl
S
S
Berger
R
R
D000328:Adult; D000368:Aged; D003114:Colony-Forming Units Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006098:Granulocytes / Q000502:physiology; D016298:Hematopoietic Cell Growth Factors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007377:Interleukin-3 / Q000502:physiology; D007943:Leukemia, Hairy Cell / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008264:Macrophages / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000502:physiology
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor