HETEROGENEITY OF THE INHIBITORY EFFECTS OF IL-4 IN 2 NOVEL B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA CELL-LINES

The present study describes two novel cell lines, DUNATIS and SILVANUS , established from B lineage acute lymphoblastic leukemia patients. Re spectively, 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 a ssociated with rapid cell death and reduction of cellularity in DUNATI S, whereas these parameters were considerably less pronounced and only observed after longer-term exposure of the SILVAN US cells to IL-4. I n addition to these differences, although both cell lines expressed FE S oncoprotein, a 100 kDa protein associated with FES was strikingly fo und to be tyrosine-phosphorylated in response to IL-4 exclusively in D UNATIS cells. These data demonstrate that IL-4 displays heterogenous e ffects on leukemic B cell precursors responsive to inhibition of DNA s ynthesis 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 f or further identification of target molecules in IL-4 signalling. (C) 1997 Elsevier Science Ltd. All rights reserved.