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


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.
Wang
Yuan-Yuan
YY
The First Affiliated Hospital, Suzhou University, Jiangsu Institute of Hematology, Leukemia Research Division, Key Laboratory of Thrombosis and Hemostasis, Ministry of Health, Suzhou 215006, China.
Cen
Jian-Nong
JN
He
Jun
J
Shen
Hong-Jie
HJ
Liu
Dan-Dan
DD
Yao
Li
L
Qi
Xiao-Fei
XF
Chen
Zi-Xing
ZX
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000753:Anemia, Refractory / Q000378:metabolism / Q000473:pathology; D000754:Anemia, Refractory, with Excess of Blasts / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D045744:Cell Line, Tumor / Q000737:chemistry / Q000473:pathology; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D005260:Female; D019942:Genes, p16; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000378:metabolism / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D012720:Severity of Illness Index; D055815:Young Adult; D001616:beta-Galactosidase / Q000032:analysis
D015415:Biomarkers; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001616:beta-Galactosidase