CD30 ligand (CD30L)-expressing acute myeloid leukemias: a new model of paracrine interactions for the regulation of blast cells proliferation.
CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals through its specific counterstructure CD30. Even though there are indications that CD30L plays a key role as a paracrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known about its biological functions in other human hemopoietic malignancies, despite the demonstration of the frequent expression of CD30L in hemopoietic neoplasms of both myeloid and lymphoid origin. The present review summarises structural and biological properties of CD30L, and focuses on CD30L+ acute myeloid leukemias (AMLs) by recapitulating some phenotypic and clinical features of this subset of acute leukemias. We also discuss some mechanisms by which CD30L-expressing leukemic blasts may gain a proliferative advantage through direct interaction with specific cells, in turn expressing its specific counterreceptor CD30. In particular, data has been provided suggesting that CD30L+ AMLs may evoke a sort of polarized T-cell response with the preferential production of Th2-like cytokines, mainly IL-4, by specific CD30-expressing T cell subsets. On the other hand, leukemic blasts presenting surface CD30L, have been shown to express a peculiar cytokine-receptors pattern that makes them an ideal target for T cells-produced Th2-like cytokines. Furthermore, some Th2-like cytokines, such as IL-4, are able to enhance blast cells proliferation, as well as to up-regulate the surface expression of specific adhesion molecules that have been shown to be associated with the presence of CD30L on AML blasts.
Gattei
V
V
Department of Medical Oncology, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano, Italy. vgattei@ets.it
Degan
M
M
Rossi
F M
FM
de Iuliis
A
A
Mazzocco
F T
FT
Serraino
D
D
Zagonel
V
V
Aldinucci
D
D
Pinto
A
A
D000208:Acute Disease; D001752:Blast Crisis / Q000276:immunology*; D053285:CD30 Ligand; D006801:Humans; D017730:Ki-1 Antigen; D007951:Leukemia, Myeloid / Q000276:immunology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000032:analysis*; D008954:Models, Biological; D019899:Paracrine Communication
D053285:CD30 Ligand; D017730:Ki-1 Antigen; D008024:Ligands; D008562:Membrane Glycoproteins; C505774:TNFSF8 protein, human