Proliferation and maturation of human leukemia cells in liquid culture

Bone marrow from patients with acute myelogenous leukemia (AML), acute myelomonocytic leukemia (AMML), chronic myelogenous leukemia (CML), preleukemia, and from healthy volunteers was cultured using a recently developed liquid diffusion technique. Differential and viable cell counts and 3H-thymidine labeling indices were performed at intervals up to 30 days. Differentiation was assessed morphologically by light and electron microscopy, histochemically, and by functional tests for phagocytosis and the presence of surface receptors for IgG. Colony-stimulating activity (CSA) was assayed against normal human bone marrow by the agar colony technique. In acute leukemia cultures, viable cell counts usually fell within the normal range. However, most AML cells failed to demonstrate significant maturation in vitro, and did not produce detectable CSA. In AMML cultures, maturation was defective but some differentiated macrophages were observed and the cells produced high concentrations of CSA. Preleukemic cultures demonstrated normal growth but maturation was impaired as evidenced by a high percentage of immature cells during the first 7 days. CML cultures showed abnormally high growth capacity resulting in viable cell counts 2-3 times normal. In the chronic phase of CML, maturation was qualitatively normal and the cells produced CSA. With the onset of blast transformation, maturation became abnormal but growth remained high. These studies support a concept of AML as a primary defect in cellular maturation and of CML as a primary abnormality of proliferation. The production of CSA by neoplastic cells relates to the degree of monocyte-macrophage differentiation within the leukemic population. Human preleukemia is characterized by a failure of normal maturation in vitro.