CD30 Ligand Is Frequently Expressed in Human Hematopoietic Malignancies of Myeloid and Lymphoid Origin

Abstract

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor α-chain, the αM (CD11b) chain of β2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.

Expression of CD30 mRNA, CD30L mRNA and a variant form of CD30 mRNA in restimulated peripheral blood mononuclear cells (PBMC) of patients with helminthic infections resembling a Th2 disease

“…In all subjects examined so far, spontaneous CD30L mRNA expression after antigenic or mitogenic stimulation could be demonstrated. These observations are in accordance with results of Gattei et al [21] showing that CD30 ligand is frequently expressed in all stages of human haematopoiesis.…”

In vitro production of anti‐RBC antibodies and cytokines in chronic lymphocytic leukemia

“…Likewise, sCD30 was increased in mitogen-stimulated cultures of B-CLL patients compared with controls, particularly in advanced stage patients. Our results are in line with previous findings indicating that this TNF-superfamily ligand is involved in B-CLL pathogenesis, both in maintaining neoplastic growth and regulating the apoptotic phenomena [35][36][37]. Notwithstanding several reports on the role of CD23 and CD30 in autoimmunity [38][39][40][41][42], our results showed no difference in sCD23 and sCD30 between B-CLL patients with or without autoimmune features.…”

Signature of B‐CLL with different prognosis by Shrunken centroids of surface antigen expression profiling

“…The IgV H mutational status was performed on 117/123 PB samples, exactly as described (Degan et al, 2004b). Briefly, total RNA, extracted, reverse-transcribed, and checked for first-strand synthesis (Gattei et al, 1997;Degan et al, 2000), was amplified using a mixture of sense primers annealing either to the V H 1 through V H 6 leader sequences or to the 5 0 end of V H 1-V H 6 FR1 utilized in conjunction with a mixture of anti-sense primers complementary to the germ line J H regions (Fais et al, 1998;Damle et al, 1999;Hamblin et al, 1999;Gurrieri et al, 2002;Krober et al, 2002;Degan et al, 2004a). The purified amplified products were cloned into plasmids and sequenced (Degan et al, 2004a;Degan et al, 2004b).…”

“…Expression of surface phenotypic markers was investigated in PB samples by flow cytometry, as previously described (Gattei et al, 1997). Surface antigens were analyzed by two-or three-color immunofluorescence by combining phycoerithrin (PE)-, fluorescein isothyocyanate (FITC)-, and allophycocyanin (APC)-conjugated monoclonal antibodies (mAbs).…”