CHARACTERIZATION OF PRIMITIVE SUBPOPULATIONS OF NORMAL AND LEUKEMIC-CELLS PRESENT IN THE BLOOD OF PATIENTS WITH NEWLY-DIAGNOSED AS WELL AS ESTABLISHED CHRONIC MYELOID-LEUKEMIA

Elevated numbers of primitive Philadelphia chromosome-positive (Ph(+)) progenitors, including long-term culture-initiating cells (LTC-IC) as wall as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which f ocused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent end occasionall y exclusive presence of circulating normal (Ph(-)) LTC-IC, often at le vels above those seen for LTC-IC in the blood of normal individuals. T he presence of detectable numbers of circulating Ph(-) LTC-IC was inde pendent of the fact that the same peripheral blood samples also contai ned elevated numbers of predominantly or exclusively Ph(+) CFC. Intere stingly, both the Ph(+) and Ph(-) LTC-IC in these samples were CD34(+) CD71(-) and variably CD38(-) and Thy-1(+), as previously documented fo r LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph(+) and Ph(-) LTC-IC in mixed pop ulations. Nevertheless, an association of these phenotypes with LTC-IC function did allow highly enriched (>5% pure) suspensions of either P h(+) or Ph(-) LTG-IC to he, obtained from selected samples of CML bloo d in which the initial LTC-IC population was either predominantly Ph() or Ph(-), respectively. These findings suggest that the mechanisms c ausing mobilization of leukemic stem cells in untreated CML patients m ay affect their normal counterparts. They also indicate a possible new source of autologous calls for the support of intensive therapy of CM L patients. Finally, they provide a method for obtaining the most high ly purified populations of Ph(+) LTC-IC described to date, This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells. (C) 1996 by The American Societ y of Hematology.