HEMATOPOIETIC INHIBITION IN HAIRY-CELL LEUKEMIA

Leukopenia, thrombocytopenia, and anemia are important features of hairy cell leukemia (HCL). They are generally considered to be due to hypersplenism and to inadequate production by bone marrow which is heavily infiltrated by the neoplastic hairy cells (HC). However, the cytopenias may also be caused by hemopoietic inhibition by cytokines derived from the mononuclear cells (MNC) of HCL. We studied the MNC of HCL with an in vitro assay for granulocyte-macrophage progenitors (CFU-GM) to search for this hemopoietic inhibitor(s) and to determine the cell source and mechanism of its production/release. We found that MNC conditioned media from 7 of 9 HCL cases exerted substantial inhibitory effect (23% to 66%) on normal marrow cells. Peak inhibitory activity was obtained in media conditioned with 10(6) MNC/ml for 90 minutes to 24 hours. Both HC and lymphocytes could release inhibitor(s) through mutually synergistic cell interactions. HC alone were inactive and lymphocytes alone were only weakly active. Mixtures of conditioned media of HC and of lymphocytes were not synergistic. The lymphocytes responsible for the inhibition were present in preparations depleted of cells bearing the cluster designation 4 antigen (CD4+) and B cells and were most likely the CD8+ T-cells. In one patient so examined, a partial reversal of inhibition was achieved by treating MNC-CM with antibodies to tumor necrosis factor (TNF)-alpha suggesting that TNF-alpha was at least partly involved in the inhibition of CFU-GM. This mechanism of cytokine release may be operative in vivo to account for the cytopenias in HCL and, if so, could alter the concept of hypersplenism in this disease.