EFFECTS OF INTERFERON-ALPHA ON L-BCGF- AND TNF-ALPHA-INDUCED PROLIFERATION OF HAIRY-CELL LEUKEMIA IN JAPAN

Interferon-alpha (IFN-alpha) is very effective in patients with hairy cell leukemia (HCL), although its mechanism of action is still unknown . To investigate this issue, we studied the in vitro response to IFN-a lpha of a variant type of HCL, recently reported by us as the Japanese variant. Their clinical response to IFN-alpha (remission rate 35.7% i n the multicenter study in Japan) was inferior to that of typical HCL (remission rate 80%; mean of previous reports). We found that both low molecular weight B-cell growth factor (L-BCGF) and tumor necrosis fac tor-alpha (TNF-alpha) induced the proliferation of HC from patients wi th the Japanese variant, as well as those with typical HCL. While, in typical HCL, IFN-alpha strongly inhibited the in vitro proliferation o f HC induced by L-BCGF and TNF-alpha, the inhibitory effect of IFN-alp ha on L-BCGF and TNF-alpha-induced proliferation was low in most Japan ese variant patients. These in vitro findings may be related to the ex tent of clinical efficacy of IFN-alpha in the Japanese variant, obtain ed in the multicenter study. Since the degree of inhibition was parall el in L-BCGF- and TNF-alpha-induced proliferation in three patients ex amined simultaneously, it appeared that the antiproliferative effect o f IFN-alpha is not specific to individual growth factors. Rather, IFN- alpha might affect fundamental growth mechanisms triggered by these fa ctors.