University of Sussex

File(s) not publicly available

The enzymatic activities of CD38 enhance CLL growth and trafficking: implications for therapeutic targeting

journal contribution
posted on 2023-06-10, 04:55 authored by T Vaisitti, V Audrito, S Serra, R Buonincontri, G Sociali, E Mannino, A Pagnani, A Zucchetto, E Tissino, C Vitale, M Coscia, C Usai, Christopher PepperChristopher Pepper, V Gattei, S Bruzzone, S Deaglio
The ecto-enzyme CD38 is gaining momentum as a novel therapeutic target for patients with hematological malignancies, with several anti-CD38 monoclonal antibodies in clinical trials with promising results. In chronic lymphocytic leukemia (CLL) CD38 is a marker of unfavorable prognosis and a central factor in the pathogenetic network underlying the disease: activation of CD38 regulates genetic pathways involved in proliferation and movement. Here we show that CD38 is enzymatically active in primary CLL cells and that its forced expression increases disease aggressiveness in a xenograft model. The effect is completely lost when using an enzyme-deficient version of CD38 with a single amino-acid mutation. Through the enzymatic conversion of NAD into ADPR (ADP-ribose) and cADPR (cyclic ADP-ribose), CD38 increases cytoplasmic Ca 2+ concentrations, positively influencing proliferation and signaling mediated via chemokine receptors or integrins. Consistently, inhibition of the enzymatic activities of CD38 using the flavonoid kuromanin blocks CLL chemotaxis, adhesion and in vivo homing. In a short-term xenograft model using primary cells, kuromanin treatment traps CLL cells in the blood, thereby increasing responses to chemotherapy. These results suggest that monoclonal antibodies that block the enzymatic activities of CD38 or enzyme inhibitors may prove therapeutically useful.


Publication status

  • Published






Springer Science and Business Media LLC



Page range


Event location


Department affiliated with

  • Clinical and Experimental Medicine Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date