MOLECULAR AND BIOLOGIC CHARACTERIZATION OF A NEWLY ESTABLISHED PHILADELPHIA-POSITIVE ACUTE LYMPHOBLASTIC-LEUKEMIA CELL-LINE (Z-33) WITH AN AUTOCRINE RESPONSE TO GM-CSF

We have recently established a new Philadelphia chromosome (Ph(1))-pos itive acute lymphoblastic leukemia (ALL) cell line, designated Z-33. T his line has L2 morphology, ultrastructural characteristics of lymphob lasts and typical B lineage surface markers identical to those observe d in the Ph(1)-positive ALL patient from whom the line was derived. In addition, a rearranged immunoglobulin heavy-chain gene (J(H)) band wa s found in Z-33 cells by Southern blot analysis, confirming B cell clo nality. Cytogenetic analysis of the cell line revealed t(9;22)(q34;q11 .2). Polymerase chain reaction (PCR)-amplified cDNA from Z-33 cells de monstrated an e(1)-a(2) BCR-ABL junction, and the p190(BCR-ABL) protei n was detected in them by the immune complex kinase assay. Z-33 cells produce interleukin (IL)-1 beta, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), tumor necrosis fa ctor (TNF)-alpha, and transforming growth factor (TGF)-beta. Neither I L-1 beta, G-CSF, TNF-alpha, nor their corresponding antibodies affecte d the cell line's growth. In contrast, anti-GM-CSF neutralizing antibo dies suppressed Z-33 colony formation, and GM-CSF stimulated it in a d ose-dependent fashion. In addition, receptor studies with biotinylated GFR-CSF demonstrated specific binding to Z-33 cells, indicating that the cells express GM-CSF receptors. Taken together, our data suggest t hat the Phl-positive Z-33 ALL cells produce GM-CSF, express GM-CSF rec eptors, and show an autocrine proliferative response to this cytokine.