A. Miyazato et al., Identification of myelodysplastic syndrome-specific genes by DNA microarray analysis with purified hematopoietic stem cell fraction, BLOOD, 98(2), 2001, pp. 422-427
Myelodysplastic syndrome (MDS) is a slowly progressing hematologic malignan
cy associated with a poor outcome. Despite the relatively high incidence of
MDS in the elderly differentiation of MDS from de novo acute myeloid leuke
mia (AML) still remains problematic. Identification of genes expressed in a
n MDS-specific manner would allow the molecular diagnosis of MDS. Toward th
is goal, AC133 surface marker-positive hematopoietic stem cell (HSC)-like f
ractions have been collected from a variety of leukemias in a large-scale a
nd long-term genomics project, referred to as "Blast Bank," and transcripto
me of these purified blasts from the patients with MDS were then compared w
ith those from AML through the use of oligonucleotide microarrays. A number
of genes were shown to he 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 signalin
g proteins. Because overexpression of Dlk may play a role in the pathogenes
is of MDS, the disease specificity of Dlk-expression was tested by a quanti
tative "realtime" polymerase chain reaction analysis. Examination of the Bl
ast 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 w
ith the Blast Bank samples is an efficient approach to extract transcriptom
e data of clinical relevance for a wide range of hematologic disorders. (C)
2001 by The American Society of Hematology.