title: Juvenile monosomy 7 syndrome: evidence that the disease originates in a pluripotent hemopoietic stem cell.
abstract: 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% (25/25). 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.
mesh_terms: D000208:Acute Disease; D001853:Bone Marrow / Q000473:pathology / Q000503:physiopathology; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7; D003114:Colony-Forming Units Assay; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007621:Karyotyping; D007938:Leukemia / Q000209:etiology; D008297:Male; D009006:Monosomy; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000235:genetics* / Q000473:pathology