Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets

• Published in: International journal of molecular sciences Vol. 23; no. 15; p. 8651
• Main Authors: Punzo, Francesca, Argenziano, Maura, Tortora, Chiara, Di Paola, Alessandra, Mutarelli, Margherita, Pota, Elvira, Di Martino, Martina, Di Pinto, Daniela, Marrapodi, Maria Maddalena, Roberti, Domenico, Rossi, Francesca
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-08-2022; MDPI
• Subjects: Acute lymphoblastic leukemia; Apoptosis; Bone cancer; Cancer therapies; Cannabinoid CB1 receptors; Cannabinoid CB2 receptors; Cannabinoids; CB2 receptors; CD9 antigen; Cell growth; Cell proliferation; Cytokines; Endocannabinoid system; Enzyme-linked immunosorbent assay; Gene expression; Immune response; Immune system; Immunotherapy; Invasiveness; Kinases; Leukemia; Lymphocytes; Medical prognosis; Pathogenesis; Pediatrics; Protein expression; Proteins; RNA sequencing; Stem cells; Stimulation; SUP-B15 cell line; Tumors; Western blotting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23158651

Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.