IDENTIFICATION OF A MALIGNANT COUNTERPART OF THE MONOCYTE-DENDRITIC CELL PROGENITOR IN AN ACUTE MYELOID-LEUKEMIA

Myeloblasts derived from the peripheral blood of a patient with acute myelogenous leukemia (ORL47) were found to represent the malignant cou nterpart of the newly elucidated monocyte-dendritic cell colony-formin g unit (mono-DC-CFU). The specific cytokine conditions required to ach ieve intermediate and terminal maturation of DCs and monocytes from th ese progenitors were defined. With tumor necrosis factor (TNF) + granu locyte-macrophage colony-stimulating factor (GM-CSF) + stem cell facto r treatment numerous colony-like clusters developed. In contrast with normal DC development, further advancement of mono-DC-CFU and terminal DC maturation from the leukemic cells were dependent on the addition of interleukin-6. Functional and phenotypic analysis showed that the c apacity to differentiate was maintained fully in the DC compartment, b ut only partially in the monocyte compartment, as judged by the lack o f CD14 surface expression. Cells found at intermediate stages of DC de velopment were potent stimulators of a mixed leukocyte reaction, a fun ction usually attributed to mature DCs. As previously shown for normal DC development, antibodies to TNF alpha and GM-CSF blocked proliferat ive responses and DC growth. The importance of these observations in t he classification of leukemias, normal DC development, and potential c linical strategies is discussed. (C) 1994 by The American Society of H ematology.