Cytogenetic studies of early myeloid progenitor compartments in Ph¹- positive chronic myeloid leukemia. II. Long-term culture reveals the persistence of Ph¹-negative progenitors in treated as well as newly diagnosed patients

Abstract

We recently showed that long-term marrow cultures can be used to demonstrate the presence of Philadelphia (Ph¹) negative progenitors in patients with newly diagnosed Ph¹-positive chronic myeloid leukemia (CML). We now report results for 6 chronic phase patients studied 5-83 mo postdiagnosis and an additional 3 newly diagnosed patients. Marrow metaphases were exclusively Ph¹-positive. Clonogenic assays revealed a minor population of Ph¹-negative progenitors in 3 cases (1 treated, 2 untreated). Long-term marrow culture adherent layers contained Ph¹- negative progenitors in 6 cases (3 treated, 3 untreated). Whenever this occurred, the Ph¹-negative population had become the only one detectable within 3-4 wk, and this was always associated with a rapid decline of the Ph¹-positive population. For 2 of the 3 cases where Ph¹- negative progenitors were not detected, there was a similar rapid decline in the Ph¹-positive population in culture. In the other case, Ph¹-positive progenitors were maintained at levels typically seen in normal long-term marrow cultures. These results suggest that chromosomally normal stem cells may persist for a considerable period in the marrow of some, but perhaps not all, patients with CML, even in the face of maintenance chemotherapy. In addition, they provide new evidence of heterogeneity in this disease, as shown by the variable ability of Ph¹-positive progenitor populations to be maintained in vitro.