Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Blood

Publication Date

15/09/2000

Volume

96

Pages

2012 - 2021

Keywords

Antigens, CD34, Cell Lineage, Chromosome Deletion, Chromosomes, Human, Pair 5, Hematopoiesis, Hematopoietic Stem Cells, Humans, Myelodysplastic Syndromes