title: Isolation and characterization of hematopoietic progenitor/stem cells in 5q-deleted myelodysplastic syndromes: evidence for involvement at the hematopoietic stem cell level.
abstract: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis and frequent progression to acute myeloid leukemia. Within MDS, 5q- syndrome constitutes a distinct clinical entity characterized by an isolated deletion of the long arm of chromosome 5 (5q-), a relatively good prognosis, and infrequent transformation to acute leukemia. The cell of origin in 5q- syndrome as well as in other 5q-deleted MDS patients has not been established, but evidence for involvement of multiple myeloid (but not lymphoid) lineages has suggested that a myeloid-restricted progenitor rather than a pluripotent (lympho-myeloid) stem cell might be the primary target in most patients. Although in 9 patients no evidence of peripheral blood T-cell and only 1 case of B-cell involvement was found, the data herein support that 5q deletions occur in hematopoietic stem cells (HSCs) with a combined lympho-myeloid potential. First, in all investigated patients a minimum of 94% of cells in the minor CD34(+)CD38(-) HSC compartment were 5q deleted as determined by fluorescence in situ hybridization. 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 early-acting cytokines, long-term culture-initiating cells, and nonobese diabetic/severe combined immunodeficiency repopulating cells supported that MDS HSCs in 5q-deleted patients are CD34(+)CD38(-), but inefficient at reconstituting hematopoiesis.
authors.affiliation: Stem Cell Laboratory, Institute of Laboratory Medicine, and the Department of Hematology, Lund University Hospital, Lund, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Nilsson
authors.forename: I
authors.initials: I
authors.lastname: Astrand-Grundström
authors.forename: I
authors.initials: I
authors.lastname: Arvidsson
authors.forename: B
authors.initials: B
authors.lastname: Jacobsson
authors.forename: E
authors.initials: E
authors.lastname: Hellström-Lindberg
authors.forename: R
authors.initials: R
authors.lastname: Hast
authors.forename: S E
authors.initials: SE
authors.lastname: Jacobsen
mesh_terms: D018952:Antigens, CD34; D019070:Cell Lineage; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology*; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*
chemical_list: D018952:Antigens, CD34