title: Adenosine Generated in the Bone Marrow Niche Through a CD38-Mediated Pathway Correlates with Progression of Human Myeloma.
abstract: Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ATP and increasing NAD+. Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD+is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH. The observed variability in adenosine concentrations in bone marrow aspirates is a result of the interactions taking place among myeloma and other cells in the bone marrow niche. A pilot study showed that adenosine profiles differ during disease progression. Adenosine levels were significantly higher in the bone marrow plasma of patients with symptomatic myeloma and correlated with ISS staging, suggesting that adenosine is produced in the myeloma niche at micromolar levels by an ectoenzymatic network centered on CD38. Adenosine levels increase with disease aggressiveness, a finding that supports adenosine as a potential marker of myeloma progression.
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino 10126, Italy.|CeRMS, University of Torino, Torino 10126, Italy.
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Horenstein
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino 10126, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Quarona
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma 43126, Italy.
authors.forename: Denise
authors.initials: D
authors.lastname: Toscani
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma 43126, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Costa
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino 10126, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Chillemi
authors.affiliation: Laboratory of Oncology, Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: Myeloma Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma 43126, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Giuliani
authors.affiliation: Laboratory of Immunogenetics, Department of Medical Sciences, University of Torino, Torino 10126, Italy.|CeRMS, University of Torino, Torino 10126, Italy.|Transplantation Immunology, Città della Salute e della Scienza, Torino 10126, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
keywords: adenosine; bone niche; clinical staging; ectoenzymes; myeloma