Cytoplasmic micro heavy chain confers sensitivity to dexamethasone-induced apoptosis in early B-lineage acute lymphoblastic leukemia.

Abstract

Most childhood acute lymphoblastic leukemia (ALL) arises from early B-lineage cells,and response to steroid treatment is critical to successful ALL therapy. To investigate the effect of the pre-B cell receptor (pre-BCR) complex on the response of leukemic cells to steroids, cytoplasmic micro protein (cyto mu) was transfected into cyto mu-, steroid-resistant early B cell lines. The presence of cyto mu and the assembled pre-BCR complex conferred sensitivity to dexamethasone-induced apoptosis. Both intrinsic and extrinsic apoptosis pathways are involved in this cell death. However, if the transfected cyto micro protein is unable to assemble the pre-BCR complex, the cells remain resistant to dexamethasone. These findings suggest a role for the pre-BCR complex in the response of ALL cells to treatment and provide insight into the mechanism of steroid response in the treatment of pre-B ALL.