Defective recloning capacity of granulocyte-macrophage colony-forming cells in chronic myeloid leukaemia.

We investigated the recloning capacity of normal and chronic myeloid leukaemia granulocyte-macrophage colony-forming cells (CFU-GM) after 7 d culture in methylcellulose. Normal CFU-GM were recloned with the formation of 3.52 +/- 1.12 secondary CFU-GM per primary d-7 colony. A frequency distribution of the colony-forming cells within d-7 colonies showed a heterogeneous distribution with the majority of d-7 colonies containing 1 or zero CFU-GM and a few colonies containing more than 30 CFU-GM. Separation of marrow cells by velocity sedimentation demonstrated that the recloning capacity was primarily expressed by the smallest colony-forming cells. In contrast, marrow or blood cells from 18 patients with Ph1-chromosome-positive CML in the chronic phase produced colonies with defective recloning capacity. Only 1 patient had a recloning value within the normal range; the others had a mean value of 0.35 (range 0-1.28) secondary colonies per primary d-7 colony. The recloning defect was not related to WBC or treatment, since 5 newly diagnosed patients with CML also showed defective recloning before any treatment was given, which is compatible with the defect being an inherent property of CML.