Cytogenetic studies of early myeloid progenitor compartments in Ph1-positive chronic myeloid leukaemia (CML). I. Persistence of Ph1-negative committed progenitors that are suppressed from differentiating in vivo.

Abstract

We have cytogenetically analysed individual haemopoietic colonies to investigate the level and extent of normal stem cell suppression that occurs in patients with Philadelphia chromosome (Ph1)-positive CML. Seventeen patients were studied at diagnosis prior to the initiation of chemotherapy and five of these were studied again 1-16 months later. Another nine patients were studied for the first time 2-96 months after diagnosis and initiation of chemotherapy. No chromosomally normal metaphases were found in either direct marrow preparations or in haemopoietic colonies obtained from simultaneous assays of marrow and/or blood samples from 20 of the 26 patients studied. In the other six, chromosomally normal haemopoietic progenitors (BFU-E, CFU-C and CFU-G/E) were readily demonstrable even though in five of these patients all dividing cells in the bone marrow appeared to belong to the Ph1-positive clone at the time of study. These results indicate that the suppressive effects of clonal expansion on normal haemopoiesis are more pronounced, and apparent sooner, in the more differentiated compartments. In addition, they support the view that the original population of normal stem cells does not disappear rapidly, although their numbers may be diluted to undetectable levels depending upon the extent of clonal expansion at the stem cell level by the time of diagnosis.