Abstract

Myelodysplastic syndrome (MDS) is a group of hematopoietic stem/progenitor cell clonal disorders characterized by dysplastic morphology of at least one cell lineage and high risk of evolution to acute myeloid leukemia (AML). Thus, it could be viewed as a preneoplastic stage prior to development of overt acute myeloid leukemia (AML). A number of studies indicated that oncogene-induced senescence as a crucial cellular response at premalignant stage can protect cells from tumor formation. Senescent cells emerged in premalignant cell population but not in malignant ones. p16INK4a have been identified as a cellular senescence-associated molecular marker. In present study, we have determined and compared the expression level of p16INK4a by quantitative RT-PCR and western blot in BM mononuclear cells (BMMNCs)/CD34+ cells among 53 patients of MDS and 12 of AML as well as 11 healthy controls. A significantly upregulated expression level of p16INK4a in MDS, while an significantly lower p16INK4a expression level in AML had been detected in comparison with that in healthy controls(<0.05). The IPSS score of these MDS patients negatively correlated with the p16INK4a expression level. To further confirm the senescent status, the cells of MDS, AML patients and healthy controls were examined by histochemical assays for the activity of senescence-associated beta galactosidase (SA-β-Gal). A weak blue stain reflecting the SA-β-Gal activity could be found in less than 10% cells from healthy controls after four days’ culture. On the contrary, a much stronger blue stain for SA-β-Gal had been detected in about 30–40% cells from MDS, and a little-to-no blue stain in AML cells. The semi-quantitative RT-PCR had demonstrated a similar pattern of SA-β-Gal expression among these three groups. Our preliminary results raise the question whether an accelerated cellular senescence in addition to apoptosis may contribute to the hematopoietic ineffectiveness and dysplastic morphology of cells in MDS, and if it could be of any implications for the progression of the disease.

Disclosures: No relevant conflicts of interest to declare.

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