Accelerated cellular senescence in myelodysplastic syndrome.

OBJECTIVE

To investigate the contribution of cellular senescence to the progression and prognosis of myelodysplastic syndrome (MDS).

MATERIALS AND

METHODS

We have analyzed the expression of p16INK4a in bone marrow mononuclear cells or CD34(+) cells from 53 patients with MDS, 12 acute myeloid leukemia (AML), and 11 healthy controls. Additionally, We have assessed quantitatively senescence-associated beta-galactosidase (SA-beta-gal) staining on bone marrow mononuclear cells from MDS and AML patients, HL60 and SHI-1 leukemia cell lines, and healthy control cells.

RESULTS

An upregulated expression of senescence-associated molecular marker p16INK4a was found in MDS compared with healthy controls, while a lower expression of p16INK4a was observed in AML compared with healthy controls. International Prognostic Scoring System score was negatively correlated with the percentage of p16INK4a-positive cells. The SA-beta-gal activity measured by mean percentage of positive cells was significantly higher in MDS cases when compared with controls. Meanwhile, percentage of SA-beta-gal-positive cells was also remarkably higher in dysplastic cells of MDS when compared to nondysplastic cells from MDS.

CONCLUSIONS

These results of our present study suggested an accelerated cellular senescence occurred in MDS, and the cellular senescence may be involved in the progression and prognosis of MDS.