چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| زینب مظلومی | سوم |
| حجت اله نوزاد چروده | چهارم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | Introduction: Acute Myeloid Leukemia (AML) is an invasive and lethal blood cancer caused by a rare population of Leukemia Stem Cells (LSCs). Telomerase activation is a limitless self-renewal process in LSCs. Apart from telomerase role in telomere lengthening, telomerase (especially hTERT subunit) inhibits intrinsic-, extrinsic-, and p53- mediated apoptosis pathways. In this study, the effect of Telomerase Inhibition (TI) on intrinsic-, extrinsic-, p53- mediated apoptosis, and DNMT3a and TET epigenetic markers in stem (CD34+) and differentiated (CD34-) AML cells is evaluated. Methods and Materials: High-purity CD34+ (primary AML and KG-1a) cells were enriched using the Magnetic- Activated Cell Sorting (MACS) system. CD34+ and CD34- (primary AML and KG-1a) cells were treated with BIBR1532 and then, MTT assay, Annexin V/7AAD, Ki-67 assay, Telomere Length (TL) measurement, and transcriptional alterations of p53, hTERT, TET2, DNMT3a were analyzed. Finally, apoptosis-related genes and proteins were studied. Results: TI with the IC50 values of 83.5, 33.2, 54.3, and 24.6 μM in CD34+ and CD34- (primary AML and KG- 1a) cells significantly inhibited cell proliferation and induced apoptosis. However, TI had no significant effect on TL. The results also suggested TI induced intrinsic-, extrinsic-, and p53- mediated apoptosis. It was shown that the expression levels of DNMT3a and TET2 epigenetic markers were highly increased following TI. Conclusion: In total, it was revealed that TI induced apoptosis through intrinsic, extrinsic, and p53 pathways and increased the expression of DNMT3a and TET2 epigenetic markers |
| کلمات کلیدی | Telomerase, Telomerase activity, AML, Apoptosis, Epigenetic marker |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| 6.pdf | 1403/10/26 | 339010 | دانلود |
| semnan.GIF | 1403/11/02 | 569247 | دانلود |
