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Persistence of myeloid progenitor cells expressing BCR-ABL mRNA after
allogeneic bone marrow transplantation for chronic myelogenous leukemia
G Pichert, EP Alyea, RJ Soiffer, DC Roy and J Ritz
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston,
MA 02115.
Previous studies have shown that tumor-specific bcr-abl mRNA can often be
detected by polymerase chain reaction. (PCR) for months to years after
allogeneic bone marrow transplantation (BMT) for chronic myelocytic
leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does
not invariably predict for clinical relapse post-BMT. This has led to the
hypothesis that bcr-abl mRNA might be expressed in cells that have lost
either proliferative or myeloid differentiation potential. To directly
characterize the cells detected by PCR in patients with CML after
allogeneic BMT, we first identified five individuals in whom PCR-positive
cells could be detected at multiple times post-BMT. Bone marrow samples
from these individuals were cultured in vitro and single erythroid,
granulocytic, and macrophage colonies, each containing 50 to 100 cells,
were examined for the presence of bcr-abl mRNA by PCR. PCR-positive myeloid
colonies could be detected in four of five individuals in marrow samples
obtained 5 to 56 months post-BMT. Overall, 7 of 135 progenitor cell
colonies (5.2%) were found to be PCR-positive. The expression of bcr-abl
mRNA appeared to be equally distributed among committed erythroid,
macrophage, and granulocyte progenitors. These patients have now been
followed-up for an additional 20 to 33 months from the time of progenitor
cell PCR analysis but only one of these individuals has been found to have
cytogenetic evidence of recurrent Ph+ cells. These results show that
long-term persistence of PCR-detectable bcr-abl mRNA after allogeneic BMT
can be caused by the persistence of CML-derived clonogenic myeloid
precursors that have survived the BMT preparative regimen. These cells
continue to have both proliferative and myeloid differentiation capacity in
vitro. Nevertheless, these PCR-positive cells do not appear to either
expand or differentiate in vivo for prolonged periods, suggesting the
presence of mechanisms for suppression of residual clonogenic leukemia
cells in vivo.
Volume 84,
Issue 7,
pp. 2109-2114,
10/01/1994
Copyright © 1994 by The American Society of Hematology

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