PERSISTENCE OF MULTIPOTENT PROGENITORS EXPRESSING AML1 ETO TRANSCRIPTS IN LONG-TERM REMISSION PATIENTS WITH T(8-21) ACUTE MYELOGENOUS LEUKEMIA/

The leukemia-specific AML1/ETO fusion gene has been shown to be detect ed by reverse transcriptase polymerase chain reaction (RT-PCR) analysi s in patients with t(8;21) acute myelogenous leukemia (AML) in long-te rm remission. In the present study, the AML1/ETO mRNA could be detecte d by RT-PCR in bone marrow (BM) and/or peripheral blood (PB) samples f rom all 18 patients who had been maintaining complete remission for 12 to 150 months (median, 45 months) following chemotherapy or PB stem c ell transplantation (PBSCT), whereas it could not be detected in four patients who had been maintaining remission for more than 30 months fo llowing allogeneic BM transplantation (BMT). We surveyed the expressio n of AML1/ETO mRNA in clonogenic progenitors from BM in these cases. N otably, 51 of 2.469 colonies from clonogenic progenitors (2.1%) expres sed the AML1/ETO mRNA in 18 cases who were RT-PCR(+) in BM and/or PB s amples. Expression was observed in various clonogenic progenitors, inc luding granulocyte-macrophage colonies, mixed colonies, erythroid colo nies, and megakaryocyte colonies. Furthermore, we analyzed the clonali ty of these progenitors by X-chromosome inactivation patterns of the p hosphoglycerate kinase (PGK) gene in four female patients. The AML1/ET O mRNA(+) progenitors showed the PGK allele identical to that detected in the leukemic blasts from the time of initial diagnosis. Normal con stitutive hematopoiesis was sustained by polyclonal BM reconstitution in these patients. Accordingly, these committed progenitor cells that express AML1/ETO mRNA during remission likely have arisen from common t(8;21)(+) pluripotent progenitor cells with at least trilineage diffe rentiation potential. These data strongly suggest that the origin of t he clonogenic leukemic progenitors of t(8;21) AML may be multipotent h ematopoietic progenitors that acquired the t(8;21) chromosomal abnorma lity. (C) 1996 by The American Society of Hematology.