Accelerated cellular senescence in myelodysplastic syndrome

Exp Hematol. 2009 Nov;37(11):1310-7. doi: 10.1016/j.exphem.2009.09.002. Epub 2009 Sep 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Anemia, Refractory / metabolism
  • Anemia, Refractory / pathology
  • Anemia, Refractory, with Excess of Blasts / metabolism
  • Anemia, Refractory, with Excess of Blasts / pathology
  • Biomarkers
  • Cell Line, Tumor / chemistry
  • Cell Line, Tumor / pathology
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Female
  • Genes, p16
  • Humans
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology*
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology*
  • Neoplasm Proteins / analysis
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Severity of Illness Index
  • Young Adult
  • beta-Galactosidase / analysis

Substances

  • Biomarkers
  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • beta-Galactosidase