Silvia Deaglio, M.D., Ph.D. University of Torino, Medical School (Italy)

BIOLOGY

CD38 and the fate of CLL cells: innocent bystander or culprit?

Update:

CD38 and ZAP-70 are two molecules acting as negative prognostic markers for CLL patients. Clinical trials have shown that a combined analysis of CD38 and ZAP-70 expression results in more efficient identification of patients with high risk CLL. The molecular basis for this observation is that CD38 and ZAP-70 are functionally linked and control growth of CLL cells. We also showed that CD38 and ZAP-70 favor migration of CLL cells from the blood to peripheral lymphoid organs (such as spleen and lymph nodes) where tumor cells are met with a microenvironment that favors growth. We have now shown that this happens because CD38 facilitates molecular responses to chemokines (such as CXCL12) which control movement of CLL cells. As a consequence, administration of anti-CD38 antibodies potently blocks migration of CLL cells, trapping them in the blood, where they are more accessible to drug attack.

This information provides the rationale for devising a CLL therapy that targets CD38. The use of reagents specifically blocking this molecule might provide a new approach for interfering with harmful growth circuits, therefore increasing the susceptibility of leukemic cells to conventional chemotherapy