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Int. J. Mol. Sci. 2018, 19(4), 1167;

Targeting the Adenosinergic Axis in Chronic Lymphocytic Leukemia: A Way to Disrupt the Tumor Niche?

Department of Medical Sciences, University of Turin School of Medicine & Italian Institute for Genomic Medicine (IIGM), via Nizza, 52, 10126 Torino, Italy
These authors equally contributed to the paper.
Author to whom correspondence should be addressed.
Received: 21 March 2018 / Revised: 6 April 2018 / Accepted: 9 April 2018 / Published: 12 April 2018
(This article belongs to the Special Issue Purinergic Signalling in Cancer and Inflammation)
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Targeting adenosine triphosphate (ATP) metabolism and adenosinergic signaling in cancer is gaining momentum, as increasing evidence is showing their relevance in tumor immunology and biology. Chronic lymphocytic leukemia (CLL) results from the expansion of a population of mature B cells that progressively occupies the bone marrow (BM), the blood, and peripheral lymphoid organs. Notwithstanding significant progress in the treatment of these patients, the cure remains an unmet clinical need, suggesting that novel drugs or drug combinations are needed. A unique feature of CLL is its reliance on micro-environmental signals for proliferation and cell survival. We and others have shown that the lymphoid niche, an area of intense interactions between leukemic and bystander non-tumor cells, is a typically hypoxic environment. Here adenosine is generated by leukemic cells, as well as by cells of myeloid origin, acting through autocrine and paracrine mechanisms, ultimately affecting tumor growth, limiting drug responses, and skewing the immune cells towards a tolerant phenotype. Hence, understanding the mechanisms through which this complex network of enzymes, receptors, and metabolites functions in CLL, will pave the way to the use of pharmacological agents targeting the system, which, in combination with drugs targeting leukemic cells, may get us one step closer to curing these patients. View Full-Text
Keywords: adenosine; ATP; chronic lymphocytic leukemia; tumor niche; immunosuppression adenosine; ATP; chronic lymphocytic leukemia; tumor niche; immunosuppression

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Vaisitti, T.; Arruga, F.; Deaglio, S. Targeting the Adenosinergic Axis in Chronic Lymphocytic Leukemia: A Way to Disrupt the Tumor Niche? Int. J. Mol. Sci. 2018, 19, 1167.

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