ON THE MATURATION ORDER OF AML CELLS - A DISTINCTION ON THE BASIS OF SELF-RENEWAL PROPERTIES AND IMMUNOLOGICAL PHENOTYPES

  • 1 January 1984
    • journal article
    • research article
    • Vol. 63  (3) , 684-689
Abstract
To investigate the heterogeneous cellular structure of human acute myeloid leukemia (AML), subpopulations of cells were distinguished by 2 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 2 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 2 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. The cell organization of AML apparently 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.