PMID- 20220779
OWN - NLM
STAT- MEDLINE
DCOM- 20100520
LR  - 20151119
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 24
IP  - 4
DP  - 2010 Apr
TI  - Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic 
      stem cells.
PG  - 756-64
LID - 10.1038/leu.2010.31 [doi]
AB  - To gain insight into the molecular pathogenesis of the myelodysplastic syndromes 
      (MDS), we performed global gene expression profiling and pathway analysis on the 
      hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 
      healthy controls. The most significantly deregulated pathways in MDS include 
      interferon signaling, thrombopoietin signaling and the Wnt pathways. Among the 
      most significantly deregulated gene pathways in early MDS are immunodeficiency, 
      apoptosis and chemokine signaling, whereas advanced MDS is characterized by 
      deregulation of DNA damage response and checkpoint pathways. We have identified 
      distinct gene expression profiles and deregulated gene pathways in patients with 
      del(5q), trisomy 8 or -7/del(7q). Patients with trisomy 8 are characterized by 
      deregulation of pathways involved in the immune response, patients with 
      -7/del(7q) by pathways involved in cell survival, whereas patients with del(5q) 
      show deregulation of integrin signaling and cell cycle regulation pathways. This 
      is the first study to determine deregulated gene pathways and ontology groups in 
      the HSC of a large group of MDS patients. The deregulated pathways identified are 
      likely to be critical to the MDS HSC phenotype and give new insights into the 
      molecular pathogenesis of this disorder, thereby providing new targets for 
      therapeutic intervention.
FAU - Pellagatti, A
AU  - Pellagatti A
AD  - LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK.
FAU - Cazzola, M
AU  - Cazzola M
FAU - Giagounidis, A
AU  - Giagounidis A
FAU - Perry, J
AU  - Perry J
FAU - Malcovati, L
AU  - Malcovati L
FAU - Della Porta, M G
AU  - Della Porta MG
FAU - Jadersten, M
AU  - Jadersten M
FAU - Killick, S
AU  - Killick S
FAU - Verma, A
AU  - Verma A
FAU - Norbury, C J
AU  - Norbury CJ
FAU - Hellstrom-Lindberg, E
AU  - Hellstrom-Lindberg E
FAU - Wainscoat, J S
AU  - Wainscoat JS
FAU - Boultwood, J
AU  - Boultwood J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100311
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Biomarkers, Tumor/*genetics/metabolism
MH  - Case-Control Studies
MH  - Chromosome Deletion
MH  - Chromosomes, Human, Pair 5/genetics
MH  - Chromosomes, Human, Pair 7/genetics
MH  - Chromosomes, Human, Pair 8/genetics
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Hematopoietic Stem Cells/*metabolism/pathology
MH  - Humans
MH  - Myelodysplastic Syndromes/*genetics/metabolism
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA, Messenger/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Signal Transduction
MH  - Trisomy
EDAT- 2010/03/12 06:00
MHDA- 2010/05/21 06:00
CRDT- 2010/03/12 06:00
PHST- 2010/03/12 06:00 [entrez]
PHST- 2010/03/12 06:00 [pubmed]
PHST- 2010/05/21 06:00 [medline]
AID - leu201031 [pii]
AID - 10.1038/leu.2010.31 [doi]
PST - ppublish
SO  - Leukemia. 2010 Apr;24(4):756-64. doi: 10.1038/leu.2010.31. Epub 2010 Mar 11.