Abstract The present study describes two novel cell lines, DUNATIS and SILVANUS, established from B lineage acute lymphoblastic leukemia patients. Respectively, DUNATIS and SILVANUS display an early pre-B cell and a pre-B cell phenotype. Spontaneous DNA replication of both cell lines was strongly inhibited by IL-4. This effect was directly mediated by IL-4 and exerted through the CD124 IL-4 receptor chain. Notably, IL-4 was associated with rapid cell death and reduction of cellularity in DUNATIS, whereas these parameters were considerably less pronounced and only observed after longer-term exposure of the SILVANUS cells to IL-4. In addition to these differences, although both cell lines expressed FES oncoprotein, a 100 kDa protein associated with FES was strikingly found to be tyrosine-phosphorylated in response to IL-4 exclusively in DUNATIS cells. These data demonstrate that IL-4 displays heterogenous effects on leukemic B cell precursors responsive to inhibition of DNA synthesis via IL-4 mediated engagement of the CD124 receptor chain. The present findings may be of use for appreciation of the effects of IL-4 in B lineage ALL, and the novel cell lines could represent a model for further identification of target molecules in IL-4 signalling.