Gene expression profiling of CD34+ cells in patients with the 5q- syndrome.
The transcriptome of the CD34+ cells was determined in a group of 10 patients with the 5q- syndrome using a comprehensive array platform, and was compared with the transcriptome of CD34+ cells from 16 healthy control subjects and 14 patients with refractory anaemia and a normal karyotype. The majority of the genes assigned to the commonly deleted region (CDR) of the 5q- syndrome at 5q31-q32 showed a reduction in expression levels in patients with the 5q- syndrome, consistent with the loss of one allele. Candidate genes showing haploinsufficiency in the 5q- syndrome included the tumour suppressor gene SPARC and RPS14, a component of the 40S ribosomal subunit. Two genes mapping to the CDR, RBM22 and CSNK1A1, showed a >50% reduction in gene expression, consistent with the downregulation of the remaining allele. This study identified several significantly deregulated gene pathways in patients with the 5q- syndrome and gene pathway analysis data supports the proposal that SPARC may play a role in the pathogenesis of the 5q- syndrome. This study suggests that several of the genes mapping to the CDR of the 5q- syndrome play a role in the pathogenesis of this disorder.
Boultwood
Jacqueline
J
LRF Molecular Haematology Unit, NDCLS, John Radcliffe Hospital, Oxford, UK. jacqueline.boultwood@ndcls.ox.ac.uk
Pellagatti
Andrea
A
Cattan
Helen
H
Lawrie
Charles H
CH
Giagounidis
Aristoteles
A
Malcovati
Luca
L
Della Porta
Matteo G
MG
Jädersten
Martin
M
Killick
Sally
S
Fidler
Carrie
C
Cazzola
Mario
M
Hellström-Lindberg
Eva
E
Wainscoat
James S
JS
D000740:Anemia / Q000235:genetics*; D018952:Antigens, CD34 / Q000235:genetics*; D016022:Case-Control Studies; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D002908:Chronic Disease; D015536:Down-Regulation; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013577:Syndrome
D018952:Antigens, CD34