FURTHER EVIDENCE FOR THE EXISTENCE OF A CLONAL PH-NEGATIVE STAGE IN SOME CASES OF PH-POSITIVE CHRONIC MYELOCYTIC-LEUKEMIA

The Ph chromosome abnormality is involved in the pathogenesis of almos t all patients with chronic myelocytic leukemia (CML). Previous studie s on the B-lymphoid cell lineage in two patients with Ph-positive CML suggest that there may also be a clonal Ph-negative stage in CML and t hat the Ph-positive stage arises by subclonal expansion. To determine whether this is a frequent or a rare occurrence, 14 additional glucose -6-phosphate dehydrogenase (G6PD)-heterozygous patients with CML were studied. In five of those patients there was a statistically significa nt excess of Ph-negative B-lymphoid cell lines expressing the same G6P D type expressed in the corresponding CML clone. In no case was an exc ess of B-lymphoid lines expressing the opposite G6PD type recovered. T hese data provide further evidence that in some patients the Ph chromo some arises in a pluripotent stem cell from a pre-existing Ph-negative clone that enjoys a growth advantage.