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Blood, 15 November 2002, Vol. 100, No. 10, pp. 3553-3560
HEMATOPOIESIS
Characterization of gene expression of CD34+ cells
from normal and myelodysplastic bone marrow
Wolf-K. Hofmann,
Sven de Vos,
Martina Komor,
Dieter Hoelzer,
William Wachsman, and
H.
Phillip Koeffler
From the Division of Hematology/Oncology, Cedars Sinai
Research Institute, Los Angeles, CA, and the Department of Pathology,
University of California at Los Angeles School of Medicine; Research
Service, Veterans Affairs San Diego Healthcare System
(VASDHS), CA, and Division of Hematology/Oncology and Cancer
Center, University of California at San Diego School of Medicine, La
Jolla; and the Department of Hematology/Oncology, University Hospital,
Frankfurt/Main, Germany.
Gene patterns of expression in purified CD34+ bone
marrow cells from 7 patients with low-risk myelodysplastic syndrome
(MDS) and 4 patients with high-risk MDS were compared with expression data from CD34+ bone marrow cells from 4 healthy control
subjects. CD34+ cells were isolated by magnetic cell
separation, and high-density oligonucleotide microarray analysis was
performed. For confirmation, the expression of selected genes was
analyzed by real-time polymerase chain reaction. Class membership
prediction analysis selected 11 genes. Using the expression profile of
these genes, we were able to discriminate patients with low-risk from
patients with high-risk MDS and both patient groups from the control
group by hierarchical clustering (Spearman confidence). The
power of these 11 genes was verified by applying the algorithm to an
unknown test set containing expression data from 8 additional patients with MDS (3 at low risk, 5 at high risk). Patients at low risk could be
distinguished from those at high risk by clustering analysis. In
low-risk MDS, we found that the retinoic-acid-induced gene (RAI3), the radiation-inducible, immediate-early response
gene (IEX1), and the stress-induced phosphoprotein 1 (STIP1) were down-regulated. These data suggest that CD34+
cells from patients with low-risk MDS lack defensive proteins, resulting in their susceptibility to cell damage. In summary, we
propose that gene expression profiling may have clinical relevance for
risk evaluation in MDS at the time of initial diagnosis. Furthermore, this study provides evidence that in MDS, hematopoietic stem cells accumulate defects that prevent normal hematopoiesis.
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