Publication Date:
2014-12-06
Description:
HSPA9, a gene located on chromosome 5q31.2, is commonly deleted in patients with myelodysplastic syndromes (MDS). MDS patients with a deletion of the long arm of chromosome 5 [del(5q)] typically present with cytopenias, including anemia, and have increased levels of apoptosis in their bone marrow contributing to ineffective hematopoiesis. Recent evidence suggests that upregulation of TP53 in MDS bone marrow cells may contribute to the cytopenias and accererated apoptosis observed in patients. While the mechanisms of TP53 activation in MDS are likely to be multifactorial, gene haploinsufficiency has been shown to contribute. Previous reports have shown that knockdown of RPS14, a chromosome 5q33.1 gene, in human CD34+ cells (or heterozygous knockout in mouse bone marrow cells) results in upregulation of TP53 and an increase in apoptosis. It is not known whether additional del(5q) candidate genes contribute to TP53 activation in del(5q)-associated MDS. In order to determine whether HSPA9 gene deletion also results in TP53 activation, we used lentiviral shRNA vectors to knockdown the expression of HSPA9 in primary human CD34+ hematopoietic progenitor cells. The HSPA9 protein level was reduced to ~20% (sh960) and ~50% (sh433) compared to the control lentiviral shRNA (shGFP). Knockdown of HSPA9 significantly inhibited the growth (fold change sh960 compared to shGFP = 0.16, p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
