Next Article in Journal
Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas
Next Article in Special Issue
Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury
Previous Article in Journal
Defining Driver DNA Methylation Changes in Human Cancer
Previous Article in Special Issue
β-Nicotinamide Adenine Dinucleotide (β-NAD) Inhibits ATP-Dependent IL-1β Release from Human Monocytic Cells
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2018, 19(4), 1167; https://doi.org/10.3390/ijms19041167

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)
Full-Text   |   PDF [8978 KB, uploaded 3 May 2018]   |  

Abstract

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
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top