DNA microarray analysis of stage progression mechanism in myelodysplastic syndrome.
Myelodysplastic syndrome (MDS) is a clonal disorder of haematopoietic stem cells. Despite the high incidence of MDS in the elderly, effective treatment of individuals in its advanced stages is problematic. DNA microarray analysis is a potentially informative approach to the development of new treatments for MDS. However, a simple comparison of 'transcriptomes' of bone marrow mononuclear cells among individuals at distinct stages of MDS would result in the identification of genes whose expression differences only reflect differences in the proportion of MDS blasts within bone marrow. Such a 'population shift' effect has now been avoided by purification of haematopoietic stem-like cells that are positive for the cell surface marker AC133 from the bone marrow of healthy volunteers and 30 patients at various stages of MDS. Microarray analysis with the AC133+ cells from these individuals resulted in the identification of sets of genes with expression that was specific to either indolent or advanced stages of MDS. The former group of genes included that for PIASy, which catalyses protein modification with the ubiquitin-like molecule SUMO. Induction of PIASy expression in a mouse myeloid cell line induced apoptosis. A loss of PIASy expression may therefore contribute directly to the growth of MDS blasts and stage progression.
Ueda
Masuzu
M
Division of Hematology, Jichi Medical School, Kawachigun, Tochigi, Japan.
Ota
Jun
J
Yamashita
Yoshihiro
Y
Choi
Young Lim
YL
Ohki
Ruri
R
Wada
Tomoaki
T
Koinuma
Koji
K
Kano
Yasuhiko
Y
Ozawa
Keiya
K
Mano
Hiroyuki
H
D000208:Acute Disease; D000753:Anemia, Refractory / Q000235:genetics; D000754:Anemia, Refractory, with Excess of Blasts / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D018450:Disease Progression; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D050828:Protein Inhibitors of Activated STAT
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT