Targeting the tumor promoting effects of adenosine in chronic lymphocytic leukemia

Crit Rev Oncol Hematol. 2018 Jun:126:24-31. doi: 10.1016/j.critrevonc.2018.03.022. Epub 2018 Mar 29.

Abstract

Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms. In this review, we focused on the multiple functions and related mechanisms of ADO signaling in CLL generation and progression.

Keywords: Adenosine; Chronic lymphocytic leukemia; Tumor microenvironment.

Publication types

  • Review

MeSH terms

  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Adenosine / physiology*
  • Carcinogens / pharmacology
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Disease Progression
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Signal Transduction / physiology
  • Tumor Microenvironment / physiology*

Substances

  • Carcinogens
  • Adenosine