Common deleted genes in the 5q- syndrome: thrombocytopenia and reduced erythroid colony formation in SPARC null mice.
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.
Lehmann
S
S
Division of Hematology/Oncology, Cedars-Sinai Medical Center, School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA. Soren.Lehmann@ki.se
O'Kelly
J
J
Raynaud
S
S
Funk
S E
SE
Sage
E H
EH
Koeffler
H P
HP
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002872:Chromosome Deletion; D004906:Erythrocyte Count; D041905:Erythroid Cells / Q000166:cytology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D018922:HL-60 Cells; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000473:pathology*; D015676:Osteonectin / Q000235:genetics*; D010976:Platelet Count; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells; D013921:Thrombocytopenia / Q000235:genetics* / Q000473:pathology*
D015676:Osteonectin