Article

Common deleted genes in the 5q- syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice.

Division of Hematology/Oncology, Cedars-Sinai Medical Center, School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Leukemia (impact factor: 9.56). 10/2007; 21(9):1931-6. DOI:10.1038/sj.leu.2404852
Source: PubMed

ABSTRACT The commonly deleted region (CDR) for the 5q- syndrome has been identified as a 1.5-megabase interval on human chromosome 5q32. We studied, by real-time reverse-transcription (RT)-PCR, the expression of 33 genes within the CDR that are known to be expressed in CD34+ hematopoietic stem cells. Genes in the 5q- samples that showed the most pronounced decrease in expression compared to non-5q- samples were: solute carrier family 36, member 1 (SLC36A1; 89% downregulated), Ras-GTPase-activating protein SH3 domain-binding (G3BP; 79%), antioxidant protein 1 (ATOX1; 76%), colony-stimulating factor-1 receptor precursor (CSF1R; 76%), ribosomal protein S14 (RPS14; 74%), platelet-derived growth factor receptor-beta (PDGFRB; 73%), Nef-associated factor 1 (TNIP1; 72%), secreted protein, acidic and rich in cysteine (SPARC; 71%), annexin VI (ANAX6; 69%), NSDT (66%) and TIGD (60%). We further studied the hematopoietic system in SPARC-null mice. These mice showed significantly lower platelet counts compared to wild-type animals (P=0.008). Although hemoglobin, hematocrit and mean corpuscular volume (MCV) were lower in mice lacking SPARC, differences were not statistically significant. SPARC-null mice showed a significantly impaired ability to form erythroid burst-forming units (BFU-E). However, no significant differences were found in the formation of erythroid colony-forming units (CFU-E), granulocyte/monocyte colony-forming units (CFU-GM) or megakaryocyte colony-forming units (CFU-Mk) in these animals. We conclude that many of the genes within the CDR associated with the 5q- syndrome exhibit significantly decreased expression and that SPARC, as a potential tumor suppressor gene, may play a role in the pathogenesis of this disease.

0 0
 · 
0 Bookmarks
 · 
18 Views
  • Source
    Article: New insights into 5q- syndrome as a ribosomopathy.
    Jillian L Barlow, Lesley F Drynan, Nicola L Trim, Wendy N Erber, Alan J Warren, Andrew N J McKenzie
    [show abstract] [hide abstract]
    ABSTRACT: Myelodysplastic Syndromes (MDS) are a heterogeneous group of acquired clonal bone marrow disorders, characterised by ineffective hematopoiesis. The mechanisms underlying many of these blood disorders have remained elusive due to the difficulty in pinpointing specific gene mutations or haplo-insufficencies, which can occur within large deleted regions. However, there is an increasing interest in the classification of some of these diseases as ribosomopathies. Indeed, studies have implicated Ribosomal Protein (RP) S14 as a strong candidate for haploinsufficiency in 5q- syndrome, a particular form of MDS. Recently, two novel mouse models have provided evidence for the involvement of both RPS14 and the p53 pathway, and specific miRNAs in 5q- syndrome. In this review we will discuss: 5q- syndrome mouse models, the possible mechanisms underlying this blood disorder with respect to the candidate genes and comparisons with other ribosomopathies and the involvement of the p53 pathway in these diseases.
    Cell cycle (Georgetown, Tex.) 11/2010; 9(21):4286-93. · 5.36 Impact Factor
  • Source
    Article: Chromosome 5q deletion is extremely rare in patients with myelofibrosis.
    Koichi Takahashi, Jorge Cortes, Sherry Pierce, Lynne Abruzzo, Hagop Kantarjian, Srdan Verstovsek
    [show abstract] [hide abstract]
    ABSTRACT: Chromosome 5q deletion can be found in rare cases of myelofibrosis (MF) but the incidence, clinical significance and response to therapies are not well studied. We retrospectively reviewed charts of 939 patients with MF and identified 8 patients [0.8%] who carried 5q deletion. Of the 8, seven had complex cytogenetic abnormalities and one had additional clone with different cytogenetic abnormality. All 8 had significant three-lineage pancytopenia. Three patients took lenalidomide and one (patient with 5q-clone) achieved long-lasting hematologic response. Two patients responded to JAK2 inhibitor therapy. MF patients with 5q deletion often have complex karyotype and poor outcome.
    Leukemia research 02/2013; · 2.36 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

1.5-megabase interval
 
5q- syndrome exhibit
 
89% downregulated
 
antioxidant protein 1
 
CD34+ hematopoietic
 
colony-stimulating factor-1 receptor precursor
 
corpuscular volume
 
deleted region
 
erythroid colony-forming units
 
form erythroid burst-forming units
 
granulocyte/monocyte colony-forming units
 
human chromosome 5q32
 
lower platelet counts
 
megakaryocyte colony-forming units
 
member 1
 
Nef-associated factor 1
 
platelet-derived growth factor receptor-beta
 
ribosomal protein S14
 
solute carrier family 36
 
SPARC-null mice
 

S Lehmann