Journal
LEUKEMIA
Volume 20, Issue 3, Pages 426-432Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404102
Keywords
matricellular glycoproteins; acute myeloid leukemia; MLL; DNA methylation
Categories
Funding
- NCI NIH HHS [CA21765, R01 CA92474, R01 CA90916, K08 CA818818] Funding Source: Medline
- NCRR NIH HHS [M01 RR 00070] Funding Source: Medline
Ask authors/readers for more resources
Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular glycoprotein with growth-inhibitory and antiangio-genic functions. Although SPARC has been implicated as a tumor suppressor in humans, its function in normal or malignant hematopoiesis has not previously been studied. We found that the leukemic cells of AML patients with MLL gene rearrangements express low to undetectable amounts of SPARC whereas normal hematopoietic progenitors and most AML patients express this gene. SPARC RNA and protein levels were also low or undetectable in AML cell lines with MLL translocations. Consistent with its tumor suppressive effects in various solid tumor models, exogenous SPARC protein selectively reduced the growth of cell lines with MLL rearrangements by inhibiting cell cycle progression from G1 to Sphase. The lack of SPARC expression in MLL-rearranged cell lines was associated with dense promoter methylation. However, we found no evidence of methylation-based silencing of SPARC in primary patient samples. Our results suggest that low or absent SPARC expression is a consistent feature of AML cells with MLL rearrangements and that SPARC may function as a tumor suppressor in this subset of patients. A potential role of exogenous SPARC in the therapy of MLL-rearranged AML warrants further investigation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available