title: CD38 and chronic lymphocytic leukemia: a decade later.
abstract: 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 proliferation of cells when tested. 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 a signaling pathway that includes ZAP-70 and ERK1/2. Finally, CD38 is under a 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 on 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 the molecule is an effective target for antibody-mediated therapy in this currently incurable leukemia.
authors.affiliation: Department of Genetics, Biology and Biochemistry, University of Torino School of Medicine, Torino, Italy. fabio.malavasi@unito.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Malavasi
authors.forename: Silvia
authors.initials: S
authors.lastname: Deaglio
authors.forename: Rajendra
authors.initials: R
authors.lastname: Damle
authors.forename: Giovanna
authors.initials: G
authors.lastname: Cutrona
authors.forename: Manlio
authors.initials: M
authors.lastname: Ferrarini
authors.forename: Nicholas
authors.initials: N
authors.lastname: Chiorazzi
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D012106:Research / Q000639:trends; D013997:Time Factors; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D051997:ADP-ribosyl Cyclase 1