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ID Dube, DK Kalousek, L Coulombel, CM Gupta, CJ Eaves and AC Eaves
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.
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| Copyright © 1984 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||