title: Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features.
abstract: The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets. The expression pattern of the key members of the endocannabinoid system was analyzed in a well-characterized MCL patient cohort and correlated to biological features. 107 tumor tissues were analyzed for the mRNA levels of cannabinoid receptors 1 and 2 (CNR1 and CNR2) and the two main enzymes regulating the endocannabinoid anandamide levels in tissue: NAPEPLD and FAAH (participating in synthesis and degradation, respectively). NAPEPLD, CNR1 and CNR2 were overexpressed while FAAH expression was reduced in MCL compared to non-malignant B-cells. Both low CNR1 and high FAAH levels correlated with lymphocytosis (p=0.016 and p=0.022, respectively) and with leukocytosis (p=0.0018 and p=0.047). Weak to moderate CNR1 levels were a feature of SOX11 negative MCL (p=0.006). Both high CNR2 and high FAAH levels correlated to anemia (p=0.0006 and p=0.038, respectively). In conclusion, the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed. This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy.
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Agata M
authors.initials: AM
authors.lastname: Wasik
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Lina
authors.initials: L
authors.lastname: Nygren
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Almestrand
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Fang
authors.initials: F
authors.lastname: Zong
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Flygare
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, SE 141 86 Stockholm, Sweden.
authors.forename: Stefanie Baumgartner
authors.initials: SB
authors.lastname: Wennerholm
authors.affiliation: Clinical Pathology, Karolinska University Hospital Solna, SE 171 76 Stockholm, Sweden.
authors.forename: Leonie
authors.initials: L
authors.lastname: Saft
authors.affiliation: Department of Hematology, Stockholm South Hospital, SE 118 83 Stockholm, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Andersson
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, SE 141 86 Stockholm, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Kimby
authors.affiliation: Division of Hematology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, SE 141 86 Stockholm, Sweden.
authors.forename: Björn E
authors.initials: BE
authors.lastname: Wahlin
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Birger
authors.initials: B
authors.lastname: Christensson
authors.affiliation: Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, SE 141 86 Stockholm, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Sander
keywords: endocannabinoid system; mantle cell lymphoma