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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
AL Petzer, CJ Eaves, PM Lansdorp, L Ponchio, MJ Barnett and AC Eaves
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
Elevated numbers of primitive Philadelphia chromosome-positive (Ph+)
progenitors, including long-term culture-initiating cells (LTC-IC) as well
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 focused primarily on
an analysis of circulating progenitors present in such patients at
diagnosis, we discovered the frequent and occasionally exclusive presence
of circulating normal (Ph-) LTC-IC, often at levels above those seen for
LTC-IC in the blood of normal individuals. The presence of detectable
numbers of circulating Ph- LTC-IC was independent of the fact that the same
peripheral blood samples also contained elevated numbers of predominantly
or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these
samples were CD34+CD71- and variably CD38- and Thy-1+, as previously
documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1
expression was useful for discriminating between Ph+ and Ph- LTC-IC in
mixed populations. Nevertheless, an association of these phenotypes with
LTC- IC function did allow highly enriched (> 5% pure) suspensions of
either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood
in which the initial LTC-IC population was either predominantly Ph+ or Ph-
, respectively. These findings suggest that the mechanisms causing
mobilization of leukemic stem cells in untreated CML patients may affect
their normal counterparts. They also indicate a possible new source of
autologous cells for the support of intensive therapy of CML patients.
Finally, they provide a method for obtaining the most highly 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.
Volume 88,
Issue 6,
pp. 2162-2171,
09/15/1996
Copyright © 1996 by The American Society of Hematology
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