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Blood, 15 July 2001, Vol. 98, No. 2, pp. 422-427
NEOPLASIA
Identification of myelodysplastic syndrome-specific
genes by DNA microarray analysis with purified hematopoietic stem
cell fraction
Akira Miyazato,
Shuichi Ueno,
Ken Ohmine,
Masuzu Ueda,
Koji Yoshida,
Yoshihiro Yamashita,
Takashi Kaneko,
Masaki Mori,
Keita Kirito,
Masaki Toshima,
Yuichi Nakamura,
Kenji Saito,
Yasuhiko Kano,
Shinpei Furusawa,
Keiya Ozawa, and
Hiroyuki Mano
From the Divisions of Functional Genomics, Hematology,
Cardiology, and Molecular Immunology, Jichi Medical School,
Kawachi-gun, Tochigi, Japan; Department of Hematology, Dokkyo
University School of Medicine, Mibu, Tochigi, Japan; and Tochigi Cancer
Center, Utsunomiya, Tochigi, Japan.
Myelodysplastic syndrome (MDS) is a slowly progressing hematologic
malignancy associated with a poor outcome. Despite the relatively high
incidence of MDS in the elderly, differentiation of MDS from de novo
acute myeloid leukemia (AML) still remains problematic. Identification
of genes expressed in an MDS-specific manner would allow the molecular
diagnosis of MDS. Toward this goal, AC133 surface marker-positive
hematopoietic stem cell (HSC)-like fractions have been collected from a
variety of leukemias in a large-scale and long-term genomics project,
referred to as "Blast Bank," and transcriptome of these purified
blasts from the patients with MDS were then compared with those from
AML through the use of oligonucleotide microarrays. A number of genes
were shown to be expressed in a disease-specific manner either to MDS
or AML. Among the former found was the gene encoding the protein
Delta-like (Dlk) that is distantly related to the Delta-Notch family of
signaling proteins. Because overexpression of Dlk may play a role in
the pathogenesis of MDS, the disease specificity of Dlk expression was
tested by a quantitative "real-time" polymerase chain reaction analysis. Examination of the Blast Bank samples from 22 patients with MDS, 31 with AML, and 8 with chronic myeloid leukemia
confirmed the highly selective expression of the Dlk gene
in the individuals with MDS. Dlk could be the first candidate molecule
to differentiate MDS from AML. The proposal is made that microarray
analysis with the Blast Bank samples is an efficient approach to
extract transcriptome data of clinical relevance for a wide range of
hematologic disorders.
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