Establishment of a cytokine-producing anaplastic large-cell lymphoma cell line containing the t(2;5) translocation: Potential role of cytokines in clinical manifestations

A permanent cell line, HSC-M1 was established from a child with advanced CD 30 (Ki-1)+ anaplastic large-cell lymphoma (ALCL). Clinical features include d irritability, fever, weight loss, tender lymphadenopathy, pneumonitis, ne utrophilia. and bone marrow erythrophagocytosis. While HSC-M1 cells exhibit ed an immunophenotype characteristic of ALCL of T-cell lineage, the cell li ne also demonstrated features of monocyte-macrophage lineage. Cytogenetic a nd polymerase chain reaction (PCR) analysis of the HSC-M1 cell line and inv olved bone marrow demonstrated the characteristic non-random chromosomal tr anslocation t(2:5)(p23:q35). Reverse transcriptase PCR for mRNA expression of cytokines and cytokine receptors showed that HSC-M1 cells expressed the message for multiple cytokines and their receptors. Measurement of cytokine levels in serum samples using enzyme-linked immuno sorbent assays showed i ncreased concentrations of several cytokines. The increased levels of some cytokines correlated with disease activity and clinical symptoms. Although spontaneous production by HSC-M1 cells of some of these cytokines was demon strated, the production of others was only detectable after stimulation wit h exogenous CD30 ligand. With few exceptions. there was good correlation be tween serum cytokine levels and cytokines produced by HSC-M1 cells. These f indings indicate that cytokine production is a feature of ALCL cells and th at some of the clinical manifestations in ALCL may result from cytokines pr oduced by either the malignant or accessory cells.