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Identification of a malignant counterpart of the monocyte-dendritic cell
progenitor in an acute myeloid leukemia
F Santiago-Schwarz, DL Coppock, AA Hindenburg and J Kern
Division of Rheumatology/Allergy, Winthrop-University Hospital, Mineola,
NY.
Myeloblasts derived from the peripheral blood of a patient with acute
myelogenous leukemia (ORL47) were found to represent the malignant
counterpart of the newly elucidated monocyte-dendritic cell colony- forming
unit (mono-DC-CFU). The specific cytokine conditions require to achieve
intermediate and terminal maturation of DCs and monocytes from these
progenitors were defined. With tumor necrosis factor (TNF) +
granulocyte-macrophage colony-stimulating factor (GM-CSF) + stem cell
factor 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 capacity
to differentiate was maintained fully in the DC compartment, but only
partially in the monocyte compartment, as judged by the lack of CD14
surface expression. Cells found at intermediate stages of DC development
were potent stimulators of a mixed leukocyte reaction, a function usually
attributed to mature DCs. As previously shown for normal DC development,
antibodies to TNF alpha and GM-CSF blocked proliferative responses and DC
growth. The importance of these observations in the classification of
leukemias, normal DC development, and potential clinical strategies is
discussed.
Volume 84,
Issue 9,
pp. 3054-3062,
11/01/1994
Copyright © 1994 by The American Society of Hematology
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