Interleukin‐3 priming in acute myeloid leukaemia patients

Summary Several studies have demonstrated that G‐CSF, GM‐CSF and, in particular, IL‐3 can effectively recruit acute myeloid leukaemia (AML) blasts into the cell cycle, resulting in a significant increase in cytosine‐arabinoside (Ara‐C) mediated cytotoxicityin vitro. Since IL‐3 has shown biological and clinical activity, we investigated the cell kinetic effects of rIL‐3 and high‐dose Ara‐C/idarubicin in three patients with refractory AML selected for the presence of chromosome 7 monosomy; this enabled differentiation between the effects of IL‐3 on leukaemic and on normal cells. Thein vivo administration of rhIL‐3 (250μ/m² d s.c. for 6–10 d) recruited AML blasts into the cell cycle in two of the three patients, and this effect resulted in an increase inin vitro growth of clonogenic cells (CFU‐L) and of their S‐phase fraction. The percentage of leukaemic cells with monosomy 7 increased only in the two cases who showed a proliferative response. Normal cells were not recruited, even when rhIL‐3 was administered for up to 10 d.In vitro studies showed an increased Ara‐C cytotoxicity on clonogenic AML cells, in particular with LL‐3 plus GM‐CSF, thus confirming the priming effects of IL‐3 in the two responding cases. The results of this study suggest that rhIL‐3 can selectively recruit leukaemic cells into the cell cycle. Although leukaemic blasts can be sensitized to Ara‐C, other mechanisms of primary blast resistance may limit the clinical benefit of kinetic‐based approaches.