Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome.
One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.
Prall
Wolf C
WC
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany. Christian.Prall@med.uni-muenchen.de.|Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University, Nussbaumstraße 20, 80336, Munich, Germany. Christian.Prall@med.uni-muenchen.de.
Czibere
Akos
A
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.|Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Grall
Franck
F
Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Spentzos
Dimitrios
D
Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Steidl
Ulrich
U
Department of Cell Biology, Albert Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Giagounidis
Aristoteles Achilles Nikolaus
AAN
Department of Hematology, Oncology, and Clinical Immunology, St Johannes Hospital, Duisburg, Germany.
Kuendgen
Andrea
A
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
Otu
Hasan
H
Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Rong
Astrid
A
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
Libermann
Towia A
TA
Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
Germing
Ulrich
U
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
Gattermann
Norbert
N
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
Haas
Rainer
R
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.
Aivado
Manuel
M
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany.|Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Boston, MA, USA.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001854:Bone Marrow Cells; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
D018952:Antigens, CD34; D051017:Apoptosis Regulatory Proteins; C099815:IER3 protein, human; D008565:Membrane Proteins; D046988:Proteasome Endopeptidase Complex