Induction of complete remission of acute myeloid leukaemia by pegylated interferon-alpha-2a in a patient with transformed primary myelofibrosis.

摘要

Type I interferons (IFN) - IFN-alpha and IFN-beta, which share the same receptor (Platanias, 2005) - have antiproliferative activity in vitro against acute myeloid leukaemia (AML) cell lines, e.g. K562, HL-60, U937 (Geng et al, 1995; Benjamin et al, 2007; Zhang et al, 2007). IFN-alpha has been investigated for the treatment of AML, where it had modest effects (Rohatiner et al, 1983). Preclinical studies revealed that a continuous exposure to type I IFN was required to durably suppress AML. Enforced constitutive expression of type I IFN suppressed the malignant behaviour of K562 (Geng et al, 1995). IFN-alpha inhibited proliferation and induced apoptosis of U937 in a dose- and time-dependent fashion (Zhang et al, 2007). In a mouse xenograft model, proliferation of HL-60 and of primary human AML cells was inhibited only when there was contin- uous stable expression of type I IFN (Benjamin et al, 2007). Subcutaneous or intravenous injections had no antileukaemic effect and were not associated with detectable or stable plasma levels of type I IFN. This can be accounted for by the short half-life of IFN and provides an explanation for the dichotomy between the marked antileukaemic effects of IFN-alpha in vitro and the disappointing effects in AML patients in vivo.