Abstract # 2055 Beta-adrenergic blockade inhibits stress-related transcriptome profiles associated with worse cancer outcomes: A randomized controlled study of propranolol in hematopoietic cell transplantation recipients

Abstract

Beta-adrenergic signaling regulates multiple molecular pathways that contribute to cancer progression; beta-adrenergic antagonists efficiently block many of these effects in animals. We previously demonstrated that hematopoietic cell transplant (HCT) patients exposed to socioeconomic stress show activation of a conserved transcriptional response to adversity (CTRA) transcriptome profile, which in turn is associated with increased relapse and decreased disease-free survival. We conducted a randomized controlled trial to evaluate whether the beta-antagonist propranolol is effective in decreasing gene expression of CTRA-related genes of 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for one week prior to transplant and 4 weeks following transplant. Blood was collected at baseline, Day −2, and Day +28. Intention-to-treat analyses assessed effects on the 53-gene CTRA indicator profile and measures of CTRA-related cellular processes. Twelve participants were randomized to the intervention group and 13 to the control arm. Relative to the control group, propranolol-treated patients showed greater decreases from baseline to Day −2 and Day +28 for both CTRA gene expression (p = .017) and bioinformatic measures of CD16- classical monocyte activation (p = .005). Propranolol-treated patients also showed up-regulation of CD34+ hematopoietic progenitor cells (p = .011). Peri-transplant administration of propranolol can down-regulate CTRA gene expression, inhibit myeloid-based cellular dynamics, and up-regulate the CD34+ cells. Ongoing follow-up and future replication studies will be required to assess impacts on clinical outcomes.