Prognostic importance of hypodiploid hemopoietic precursors in myelodysplastic syndromes

It has been suggested that a poor prognosis and the development of leukemia in patients with myelodysplasia may be related to chromosomal abnormalities. We measured the DNA content of bone marrow cells with flow cytometry in 19 hematologically normal subjects and in 70 patients who had recently been diagnosed as having myelodysplasia. Thirty-four of the patients were found to have aneuploidy. This was not related to the percentage of blast cells in the bone marrow, and there was no demarcation in terms of DNA content between patients with a high percentage of blast cells and those with a low percentage of such cells. Patients with hypodiploid marrow cells had a significantly shorter survival time than other patients (P = 0.001). Patients with hyperdiploid marrow and those whose marrow had a normal DNA content had similar survival times. Hypodiploidy appears to be a better indicator of poor survival than the marrow blast-cell count. Patients with sideroblastic anemia invariably had cells with a normal or high DNA content; none of these patients died during the study. Our data suggest that there is a relation between the loss of chromosomal material and progression toward a leukemic phenotype. It is tempting to speculate that this process may involve a loss of negative regulatory genes ("anti-oncogenes").