Table 1.

Evidence for impact of β-adrenergic signaling in patients with myeloma (rows 1–5) or continuous human myeloma cell lines (rows 6–10).

Type of investigation	Main finding or clinical question	Year published	Ref.
Retrospective outcome analysis	In patients with multiple myeloma, β-blocker intake is associated with reduced disease-specific death and overall mortality	2017	5
Meta-analysis of prospective cohort studies	Psychological distress (depression, anxiety) results in 2-fold increase in disease-specific mortality	2017	12
Clinical pilot study (NCT01899326)	Stimulation of adrenergic activity by tricyclic antidepressant desipramine enhances HSC a mobilization induced by G-CSFb	2017	54
Clinical pilot study (NCT02420223)	Do patients with myeloma that undergo HSC transplantation benefit from anti-adrenergic treatment with propranolol?	2018	6
Phase 2 biomarker trial (NCT02420223)	In patients with myeloma undergoing HSC transplantation, treatment using unspecific β-blocker propranolol inhibits conserved transcriptional response to adversity (CTRA)	2020	7
Preclinical in vitro study using one HMCLc	Norepinephrine (noradrenaline) stimulates interleukin 6 (IL-6) dependent FLAM-76 myeloma cells	2008	23
High-throughput drug interaction study in vitro	β2ARd agonists synergize with backbone myeloma drugs in myeloma cell killing	2012	24
Preclinical in vitro study using one HMCL	Propanol inhibits growth and promotes apoptosis of U266 myeloma cells	2013	21
Preclinical in vitro study using three HMCLs	β1ARe agonist dobutamine inhibits myeloma in a MAPK f dependent manner	2016	25
Preclinical in vitro study using one HMCL	Epinephrine (adrenaline) enhances growth, proliferation and chemoresistance of U266 myeloma cells	2017	22

^aHematopoietic stem cell.

^bGranulocyte-colony stimulating factor.

^cHuman myeloma cell line.

^dβ2 adrenergic receptor.

^eβ1 adrenergic receptor.

^fMitogen-activated protein kinase.