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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2012-2021
PLENARY PAPER
Isolation and characterization of hematopoietic progenitor/stem
cells in 5q-deleted myelodysplastic syndromes: evidence for
involvement at the hematopoietic stem cell level
Lars Nilsson,
Ingbritt Åstrand-Grundström,
Ingrid Arvidsson,
Björn Jacobsson,
Eva Hellström-Lindberg,
Robert Hast, and
Sten E. W. Jacobsen
From the Stem Cell Laboratory, Institute of Laboratory
Medicine, and the Department of Hematology, Lund University Hospital,
Lund; Division of Hematology, Department of Medicine, and Department of
Pathology, Karolinska Hospital, Karolinska Institutet, Stockholm; and
Division of Hematology, Department of Medicine, Huddinge University
Hospital, Huddinge, Sweden.
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.
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