Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorde rs characterized by ineffective hematopoiesis and frequent progression to a cute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clin ical entity characterized by an isolated deletion of the long arm of chromo some 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q syndrome as well as in other Bq-d eleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloi d-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cel l might be the primary target in most patients. Although in 9 patients no e vidence of peripheral blood T-cell and only 1 case of B-cell involvement wa s found, the data herein support that 5q deletions occur in hematopoietic s tem cells (HSCs) with a combined lymphomyeloid potential. First, in all inv estigated patients a minimum of 94% of cells in the minor CD34(+)CD38(-) HS C compartment were 5q deleted as determined by fluorescence in situ hybridi zation. Second, in 3 of 5 patients 5q aberrations were detected in a large fraction (25% to 90%) of purified CD34(+)CD19(+) pro-B cells. Furthermore, extensive functional characterization with regard to responsiveness to earl y-acting cytokines, long-term culture-initiating cells, and nonobese diabet ic/severe combined immunodeficiency repopulating cells supported that MDS H SCs in 5q-deleted patients are CD34(+)CD38(-), but inefficient at reconstit uting hematopoiesis. (Blood. 2000; 96:2012-2021) (C) 2000 by The American S ociety of Hematology.