B lymphoproliferative diseases: Effective treatment, inhibited progression, and potential cures through isoform-specific targeting of the prolactin receptor.

Abstract

In this chapter, we describe a potential new approach to treat lymphoproliferative diseases through isoform-specific knockdown of the long form of the prolactin receptor. The chapter includes a summary of the clinical and experimental links between prolactin and such diseases and presents sufficient background about prolactin and its receptors to explain the rationale for our approach. This background also aims to explain why clinical correlations between circulating prolactin and lymphoproliferative diseases may not appear as great as perhaps they are. In the final sections, we summarize our experimental evidence supporting the use of a splice-modulating oligomer that specifically targets the long form of the prolactin receptor. The work used mouse models of systemic lupus erythematosus and diffuse large B-cell lymphoma, human databases, and normal and malignant human cells. We also refer to previous and current studies using the splice-modulating oligomer which demonstrate its lack of toxicity, including in normal immune cells. For each section, we provide a take-home message in bold font so that the reader has the option to focus briefly or delve into details supporting the take-home message.