CD38 and chronic lymphocytic leukemia: a decade later

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BlankCD38 and chronic lymphocytic leukemia: a decade later.

F Malavasi, S Deaglio, R Damle, G Cutrona, M Ferrarini, and N Chiorazzi

Blood, July 15, 2011

Department of Genetics, Biology and Biochemistry, University of Torino School of

Medicine, Torino, Italy;

This review highlights a decade of investigations into the role of CD38 in CLL.

CD38 is accepted as a dependable marker of unfavorable prognosis and as an

indicator of activation and possibly proliferation of CLL cells at the time of

analysis. Leukemic clones with higher numbers of CD38(+) cells are more

responsive to BCR signaling and are characterized by enhanced migration. In

vitro activation through CD38 drives CLL proliferation and chemotaxis, via

activation of a signaling pathway that includes ZAP-70 and ERK1/2. Finally, CD38

is under tight, polymorphic transcriptional control after external signals.

Consequently, CD38 appears to be a global molecular bridge to the environment,

promoting survival/proliferation over apoptosis. Together, this evidence

contributes to the current view of CLL as a chronic disease in which the host's

microenvironment promotes leukemic cell growth and also controls the sequential

acquisition and accumulation of genetic alterations. This view relies upon the

existence of a set of surface molecules, including CD38, which support

proliferation and survival of B cells on their way to and after neoplastic

transformation. The second decade of studies on CD38 in CLL will tell if this

marker is a novel and effective target for antibody-mediated therapy in this

currently incurable leukemia.

PMID: 21765022