CD30 LIGAND IS FREQUENTLY EXPRESSED IN HUMAN HEMATOPOIETIC MALIGNANCIES OF MYELOID AND LYMPHOID ORIGIN

CD30 ligand (CD30L) is a type-ii membrane glycoprotein capable of tran sducing 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-act ing surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic signi ficance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the ant i-CD30L monoclonal antibody M80, we were able to show that human hemat opoietic malignancies of different lineage and maturation stage displa y a frequent and broad expression of the ligand. CD30L mRNA and surfac e 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 latte r group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymph oma (B-NHL) expressed a higher surface density of CD30L as compared wi th B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified p lasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was fou nd in T-cell tumors that was mainly confined to neoplasms with an acti vated peripheral T-cell phenotype, such as T-cell prolymphocytic leuke mia, 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 pre sence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta 2 integrins, and the intercellular adhesion molecule-1 (CD54), Analys is of normal hematopoietic cells evidenced that, in addition to circul ating and tonsil B cells, a fraction of bone marrow myeloid precursors , erythroblasts, and subsets of megakaryocytes also express CD30L. Fin ally, we have shown that native CD30L expressed on primary leukemic ce lls is functionally active by triggering both mitogenic and antiprolif erative signals on CD30(+) target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering theref ore unlikely a CD30-CD30L autocrine loop in human hematopoietic neopla sms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulat ory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30(+) immune effecters and/or microenviron mental accessory cells. (C) 1997 by The American Society of Hematology .