期刊
LEUKEMIA
卷 21, 期 9, 页码 1931-1936出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404852
关键词
myelodysplastic syndrome; 5q-syndrome; SPARC
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), RasGTPase- 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- b ( 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 wildtype animals ( P 0.008). Although hemoglobin, hematocrit and mean corpuscular volume ( MCV) were lower in mice lacking SPARC, differences were not statistically significant. SPARCnull 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 colonyforming units ( CFU- E), granulocyte/ monocyte colony- forming units ( CFU- GM) or megakaryocyte colony- forming units ( CFUMk) 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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