A possible correlation between growth-factor sensitivity and response to mitoxantrone treatment in a murine myeloid...

SA7 murine myeloid leukaemia cells usually respond to stimulation in vitro by WEHI-conditioned medium by displaying increased dose-dependent proliferation. However, at recurrence following in vivo treatment of the leukaemia with mitoxantrone, the leukaemia cells developed significant insensitivity (p = 0.04) to stimulation by WEHI-conditioned medium. This altered growth-factor sensitivity was detected when two different assays were used. The recurrent leukaemic cells were morphologically indistinguishable from untreated leukaemic cells, but in normal mice they regained sensitivity to growth factors after a single transplant. The recurrent leukaemic cells were significantly resistant to some concentrations of mitoxantrone in vitro (p = 0.012). The magnitude of this resistance was mainly a function of the dose of mitoxantrone used in the initial treatment of the leukaemia. These data suggest an association between growth-factor sensitivity and response to mitoxantrone treatment including the development of resistance in the SA7HD murine myeloid leukaemia cell line.