Cytoplasmic Heavy Chain Confers Sensitivity to Dexamethasone-induced Apoptosis in Early B-lineage Acute Lymphoblastic Leukemia

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 (preBCR) complex on the response of leukemic cells to steroids, cytoplasmic protein (cyto ) was transfected into cyto -, steroid-resistant early B cell lines. The presence of cyto 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 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