Lehmann S, O'Kelly J, Raynaud S, Funk SE, Sage EH, Koeffler HP.. Common deleted genes in the 5q- syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice. Leukemia 21: 1931-1936

Division of Hematology/Oncology, Cedars-Sinai Medical Center, School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Leukemia (Impact Factor: 10.43). 10/2007; 21(9):1931-6. DOI: 10.1038/sj.leu.2404852
Source: PubMed


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.

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Available from: Emily Helene Sage, Mar 13, 2015
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    • "Genes in the commonly deleted region of chromosome 5q that are implicated in the pathogenesis of del(5q) MDS [19, 20, 25, 26, 66–68]. del(5q) deletion of the long arm of chromosome 5, MDS myelodysplastic syndromes "
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    • "Role of SPARC in 5q-Syndrome. Lehmann et al. [32] further studied the hematopoietic system in SPARC-null mice. These mice showed significantly lower platelet counts compared to wild-type animals. "
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    ABSTRACT: Myelodysplastic syndrome (MDS) with interstitial deletion of a segment of the long arm of chromosome 5q [del(5q)] is characterized by bone marrow erythroid hyperplasia, atypical megakaryocytes, thrombocythemia, refractory anemia, and low risk of progression to acute myeloid leukemia (AML) compared with other types of MDS. The long arm of chromosome 5 contains two distinct commonly deleted regions (CDRs). The more distal CDR lies in 5q33.1 and contains 40 protein-coding genes and genes coding microRNAs (miR-143, miR-145). In 5q-syndrome one allele is deleted that accounts for haploinsufficiency of these genes. The mechanism of erythroid failure appears to involve the decreased expression of the ribosomal protein S14 (RPS14) gene and the upregulation of the p53 pathway by ribosomal stress. Friend leukemia virus integration 1 (Fli1) is one of the target genes of miR145. Increased Fli1 expression enables effective megakaryopoiesis in 5q-syndrome.
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