NAD+-metabolizing ecto-enzymes shape tumor-host interactions: the chronic lymphocytic leukemia model

FEBS Lett. 2011 Jun 6;585(11):1514-20. doi: 10.1016/j.febslet.2011.04.036. Epub 2011 Apr 19.


Nicotinamide adenine dinucleotide (NAD(+)) is an essential co-enzyme that can be released in the extracellular milieu. Here, it may elicit signals through binding purinergic receptors. Alternatively, NAD(+) may be dismantled to adenosine, up-taken by cells and transformed to reconstitute the intracellular nucleotide pool. An articulated ecto-enzyme network is responsible for the nucleotide-nucleoside conversion. CD38 is the main mammalian enzyme that hydrolyzes NAD(+), generating Ca(2+)-active metabolites. Evidence suggests that this extracellular network may be altered or used by tumor cells to (i) nestle in protected areas, and (ii) evade the immune response. We have exploited chronic lymphocytic leukemia as a model to test the role of the ecto-enzyme network, starting by analyzing the individual elements that make up the whole picture.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ADP-ribosyl Cyclase 1 / chemistry
  • ADP-ribosyl Cyclase 1 / metabolism*
  • Animals
  • Extracellular Space / metabolism
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology*
  • Leukemia, Lymphocytic, Chronic, B-Cell / metabolism
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Models, Biological*
  • NAD / metabolism*


  • NAD
  • ADP-ribosyl Cyclase 1