The capacity of alpha-interferon (alpha-IFN) to induce lymphokine activated killer (LAK) cytotoxicity in the absence of interleukin-2 (IL2) has prompted us to test whether or not its ability to reduce dramatically the number of Ph1+ clones in chronic myelogenous leukaemia (CML) patients is in part mediated through the generation of natural killer (NK) or LAK activity. The latter were tested using NK-sensitive (K562) and NK-resistant (Raji) cell lines in a target-cell colony-growth inhibition assay. Effector cells (E) were patient blood mononuclear cells (MC) without in vitro activation prior to their coculture with targets (T). Out of 16 patients tested so far, three failed to undergo cytogenetic remission under alpha-IFN therapy. No NK nor LAK cells could be detected in the MC from two of them while the other displayed NK activity within upper normal limits. 13 patients underwent complete (eight) or partial (five) cytogenetic remission together with significantly high NK and/or LAK activity as compared to normal controls. These observations could favour the hypothesis of an indirect effect of alpha-IFN on leukaemic cells, mediated by cells involved in immune surveillance.

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The present study has attempted to further delineate the growth factor requirements of peripheral blasts of a patient with CML in acute phase. Phenotypic analysis of leukemic blasts from this patient before culture has shown a homogenous population of CD34+ cells at the onset of blast crisis. In the second and third samples the percentage of CD34+ DR+ blast cells decreased slightly and up to 32% of cells in the third sample expressed the CD19 antigen. Optimal proliferation of cells derived from the first sample required the presence of exogenous sCD23 and to a lesser extent IL7. The stimulatory effects of sCD23 and IL7 were clearly reduced 4 months later and no longer detected after 6 months. This variability in growth factor response along with disease progression may be related to phenotypic differentiation. There was no evidence for lymphoid or myeloid maturation after 4 days of liquid culture. Our results in conjunction with previous studies are in agreement with sCD23-involvement in the complex control of proliferative processes at both normal and leukemic stages, demonstrating that cytokines are critical in determining CML cell proliferation.