On the maturation order of AML cells: a distinction on the basis of
self-renewal properties and immunologic phenotypes
R Wouters and B Lowenberg
To investigate the heterogeneous cellular structure of human acute myeloid
leukemia (AML), subpopulations of cells were distinguished by two combined
criteria: proliferation and differentiation. Purified blast cells were
fractionated from blood or bone marrow of patients with newly diagnosed AML
and colonies and clusters grown in phytohemagglutinin (PHA)-leukocyte
feeder cultures. Large colonies, small colonies, macroclusters, and
microclusters were recloned separately to assess the replicative capacities
as a function of clone size. Large colonies showed higher proliferative
capacities than did small ones, etc. Anti-Ia and an antigranulocyte (B4.3)
monoclonal antibody (MoAb) were then employed to evaluate the stage of
differentiation of AML cells in two patients before and following colony
culture. Alterations of the immunologic phenotypes appeared during colony
formation. This suggested differentiation of cells to more mature B4.3
granulocyte antigen-positive stages. MoAb-dependent cell lysis with the two
antibodies was subsequently performed to assess the phenotypes of the
precursors of the colonies and clusters. Leukemic colony-forming cells were
Ia-positive and B4.3-negative and different from cluster-forming cells,
which were largely Ia-negative and B4.3- negative. These data suggest that
the cell organization of AML fits a maturation scheme containing immature
cells with relatively high proliferative capacities, intermediate cells
with low proliferative capacities, and end cells that are nonreplicative,
and each with specific phenotypes.
Volume 63,
Issue 3,
pp. 684-689,
03/01/1984
Copyright © 1984 by The American Society of Hematology
