F. Santiagoschwarz et al., IDENTIFICATION OF A MALIGNANT COUNTERPART OF THE MONOCYTE-DENDRITIC CELL PROGENITOR IN AN ACUTE MYELOID-LEUKEMIA, Blood, 84(9), 1994, pp. 3054-3062
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.