Juvenile monosomy 7 syndrome: evidence that the disease originates in a pluripotent hemopoietic stem cell.

The present study was undertaken to investigate the hemopoietic cell from which malignant change evolves in juvenile dyshemopoiesis with monosomy 7. Two male patients, aged 18 and 5 months, were studied using progenitor assays combined with cytogenetics. Both had hepatosplenomegaly, cytopenias and a cellular marrow. The karyotype in direct marrow was 45,XY−7/47,XY,+8/46,XY in patient 1 and 45,XY,−7/46,XY in patient 2. Patient 1 received chemotherapy but developed acute nonlymphocytic leukemia after 17 months and died 20 months after diagnosis. During this time marrow metaphases with 45,XY,−7 increased to 100% (2525). Patient 2 received an allogeneic marrow transplant 4 months after diagnosis which did not engraft. In both patients progenitors of both small (CFU-E) and large (BFU-E) erythroid colonies were present at normal frequencies. However, the colonies produced were small and poorly hemoglobinized with some erythropoietin-independent maturation. Progenitors of large granulocyte/macrophage colonies (CFU-GM) were present at an elevated frequency in the marrow of patient 1 and in the blood all progenitor classes were markedly increased. Cytogenetic analysis of colonies from this patient showed BFU-E to be 45,XY,−7 or 47,XY,+8 and CFU-GM to be 45,XY,−7 or 47,XY,+8 or 46,XY. In patient 2, most BFU-E were 45,XY,−7, although a few were 46,XY. These data indicate that malignant change in this disease involves hemopoietic stem cells capable of erythroid and in at least some cases, myeloid differentiation.