PERSISTENCE OF MYELOID PROGENITOR CELLS EXPRESSING BCR-ABL MESSENGER-RNA AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA

Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction (PCR) for months to years af ter allogeneic bone marrow transplantation (BMT) for chronic myelocyti c leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT. This has l ed to the hypothesis that bcr-abl mRNA might be expressed in cells tha t have lost either proliferative or myeloid differentiation potential. To directly characterize the cells detected by PCR in patients with C ML 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 singl e 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 indivi duals in marrow samples obtained 5 to 56 months post-BMT. Overall, 7 o f 135 progenitor cell colonies (5.2%) were found to be PCR-positive. T he expression of bcr-abl mRNA appeared to be equally distributed among committed erythroid, macrophage, and granulocyte progenitors. These p atients have now been followed-up for an additional 20 to 33 months fr om the time of progenitor cell PCR analysis but only one of these indi viduals has been found to have cytogenetic evidence of recurrent Ph(+) cells. These results show that long-term persistence of PCR-detectabl e bcr-abl mRNA after allogeneic BMT can be caused by the persistence o f 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 viv o for prolonged periods, suggesting the presence of mechanisms for sup pression of residual clonogenic leukemia cells in vivo. (C) 1994 by Th e American Society of Hematology.