A NEW CYTOKINE-DEPENDENT MONOBLASTIC CELL-LINE WITH T(9-11)(P22-Q23) DIFFERENTIATES TO MACROPHAGES WITH MACROPHAGE-COLONY-STIMULATING FACTOR (M-CSF) AND TO OSTEOCLAST-LIKE CELLS WITH M-CSF AND INTERLEUKIN-4

Monocytes/macrophages exert a series of important functions in vivo. T o facilitate detailed investigation of their functional capacity and t he mechanism leading to their differentiation, several cell lines have been established from primary material. We present here a new human m onoblastic cell line, designated UG3. UG3 cells are characterized by t he following features. (1) UG3 cells harbor the t(9;11)(p22; q23) tran slocation that results in fusion of the MLL and the AF9 genes and prod uce the corresponding AF9-MLL and MLL-AF9 fusion transcripts. (2) UG3 cells rely on the presence of exogenous growth factors for viability a nd proliferation, such as interleukin-3 (IL-3); granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony stimulating fa ctor (G-CSF), or macrophage colony-stimulating factor (M-CSF). (3) Whe n cultured in the presence of G-CSF, UG3 cells differentiate along the granulocytic lineage, as evidenced by segmentation of nuclei and posi tive staining for neutrophilic alkaline phosphatase and peroxidase. (4 ) When cultured in the presence of GM-CSF or M-CSF, UG3 cells differen tiate into mature macrophages while preserving surface expression of C D14 and CD68 and also start to release cytokines into cell-culture sup ernatants. Under these culture conditions, UG3 cells also take up acet ylated LDL. (5) When cultured in the presence of M-CSF and IL-4, UG3 c ells differentiate into osteoclast-like multinucleated giant cells cap able of bone resorption and display tartrate-resistant acid phosphatas e (TRAP) activity. UG3 cells thus provide features to qualify them as a useful model to further investigate the mechanism underlying these p rocesses and also to further elucidate the functional role of mature m onocytes/macrophages or osteoclasts. (C) 1998 by The American Society of Hematology.