We have investigated the clonality of Ph1-negative hemopoietic progenitor cells appearing in long-term marrow cultures established with cells from a mosaic Turner syndrome patient (46,XX/45,X) with Ph1- positive chronic myeloid leukemia (CML). The Ph1-positive clone had been shown previously to have arisen from a cell of the 45,X lineage. At the time of the present study, the patient was five years post- diagnosis and had been off chemotherapy for two months following a year of treatment for lymphoid blast crisis. All analyzed unstimulated marrow metaphases and each of 23 individually analyzed erythroid and granulocyte colonies produced in assays of the starting marrow were 45,X,Ph1. Pooled granulocyte colonies from the same assays yielded four metaphases that were 45,X,Ph1 and one that was 46,XX. Very few hemopoietic progenitors were detected in long-term cultures at any time; however, all of four individually analyzed large granulocyte colonies and a pooled granulocyte colony preparation obtained from assays of 4- to 6-week-old adherent layers yielded exclusively 46,XX metaphases. These results provide evidence that non-clonal progenitors can persist in patients with CML, even after the onset and treatment of blast crisis, and that the long-term marrow culture system provides a sensitive method for detecting such cells.

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