CHARACTERIZATION OF A VITAMIN-D-3-RESISTANT HUMAN CHRONIC MYELOGENOUS LEUKEMIA-CELL LINE

A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D-3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D-3, the resistant cells (JMRD(3)) continue to proliferate in the presence of 100 nmol/L vitamin D-3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D-3, and both express the retinoblastoma gene product (p110(Rb)). Vitamin D-3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110(Rb) protein, as well as its phosphorylation. In contrast, vitamin D-3 treatment of JMRD(3) had no effect on p110(Rb) expression or phosphorylation. Both RWLeu-4 and JMRD(3) express similar vitamin D-3 receptors and vitamin D-3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D-3 receptors as determined by electrophoretic mobility shift studies, However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D-3 receptor activation is altered in JMRD(3) that partially separates vitamin D-3-induced inhibition of proliferation from the induction of differentiation. (C) 1994 by The American Society of Hematology.