In Vitro Colony Formation by Normal and Leukemic Human Hematopoietic Cells: Characterization of the Colony-Forming Cells 2

Abstract

Agar cultures of blood and marrow cells were used to determine the nature and frequency of granulocytic progenitor cells (in vitro colony-forming cells) in 133 patients with various hematologic diseases, including 33 with acute and 17 with chronic myeloid or myelomonocytic leukemia. Cultures from patients with acute myeloid leukemia (AML) in relapse or in the acute transformation phase of chronic myeloid leukemia (CML) were characterized by lack of normal colony formation and either complete absence of in vitro proliferative capacity or production of large numbers of small clusters composed of poorly differentiated cells. Patients with CML had greatly increased numbers of colony-forming cells particularly in the blood, and these were identified cs myeloblast-like cells with a cloning efficiency of at least 60%. The leukemic cells grown from every patient in this study were responsive to stimulation by the specific regulator, colony-stimulating factor, supplied in culture by underlayers of normal peripheral blood cells. Leukemic colony-forming cells had an abnormally light buoyant density and low suiciding index with tritiated thymidine. Remission in both AML and CML was associatedwith a return to normal in the location, incidence, buoyant density, and suiciding index of colony-forming cells. Density separation may make it possible to separate normal from leukemic progenitor cells for therapeutic purposes.