Identification of protein-coding and non-coding RNA expression profiles in CD34+ and in stromal cells in refractory anemia with ringed sideroblasts.
BACKGROUND
Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Non-coding RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease.


METHODS
In this study, gene expression profiles of CD34+ cells of 4 patients with MDS of refractory anemia with ringed sideroblasts (RARS) subgroup and stromal cells of 3 patients with MDS-RARS were compared with healthy individuals using 44 k combined intron-exon oligoarrays, which included probes for exons of protein-coding genes, and for non-coding RNAs transcribed from intronic regions in either the sense or antisense strands. Real-time RT-PCR was performed to confirm the expression levels of selected transcripts.


RESULTS
In CD34+ cells of MDS-RARS patients, 216 genes were significantly differentially expressed (q-value <or= 0.01) in comparison to healthy individuals, of which 65 (30%) were non-coding transcripts. In stromal cells of MDS-RARS, 12 genes were significantly differentially expressed (q-value <or= 0.05) in comparison to healthy individuals, of which 3 (25%) were non-coding transcripts.


CONCLUSIONS
These results demonstrated, for the first time, the differential ncRNA expression profile between MDS-RARS and healthy individuals, in CD34+ cells and stromal cells, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes.
Baratti
Mariana O
MO
Department of Internal Medicine, School of Medical Science, Hematology and Hemotherapy Center, University of Campinas, 13083-970 Campinas, SP, Brazil.
Moreira
Yuri B
YB
Traina
Fabiola
F
Costa
Fernando F
FF
Verjovski-Almeida
Sergio
S
Olalla-Saad
Sara T
ST
D000368:Aged; D000753:Anemia, Refractory / Q000150:complications / Q000235:genetics*; D000756:Anemia, Sideroblastic / Q000150:complications / Q000235:genetics*; D018952:Antigens, CD34 / Q000378:metabolism*; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
D018952:Antigens, CD34; D011506:Proteins; D022661:RNA, Untranslated