Secreted protein, acidic and rich in cysteine (SPARC), is a matricellular 
glycoprotein with growth-inhibitory and antiangiogenic 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 S phase. 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.