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Document Type |
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Thesis |
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Document Title |
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The Transcriptional effect of ATRA and Vitamin D differentiation agent on AML cell line التأثير النسخي لحمض الريتنويك وفيتامين د المسؤولة عن العلاج التطوري على خط خلايا سرطان الدم الحاد |
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Subject |
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Faculty of Applied Medical Sciences |
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Document Language |
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Arabic |
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Abstract |
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Differentiation-based-therapy that based upon promoting the differentiation of arrested blast cells in AML is a well-known approach that is given much attention as an alternative therapy for acute myeloid leukemias. ATRA and VIT-D3 are widely used examples of differentiation agents that direct the cells toward granulocytic and monocytic lineages. Previous studies using ATRA and VIT-D3 focused on the changes that occurred at the protein level, cell surface marker level or morphology with less attention given to the changes made at mRNA level. Therefore, many questions remained unanswered regarding the underlying transcriptional regulation that instructs the differentiation of AML cells to granulocytes and monocytes. In this study, the expression level of maturation genes and transcription factors were measured in HL-60 AML cell line treated with ATRA and with VIT-D3 at different time points. Our results demonstrated that using 1µM ATRA showed increase in CD11b granulocyte marker, together with SPI1 and CEBPα transcription factors that are the master regulator of monocytic and granulocytic cells, respectively. Interestingly, some of the monocytic genes encoding for monocyte differentiation (CD14, CD11c, CD33, and CD4) were upregulated as well and showed a significant correlation with SPI1 in response to ATRA showing a tendency to commit and differentiate to monocytic lineage. On the other hand, in response to 10nM VIT-D3: CD14, CD68, CD11c, and CD11b were upregulated together with RUNX1 and SPI1 but not CEBPα. The upregulation in CD14 and CD11c positively correlate with RUNX1 transcription factor. Our data shows how ATRA and VIT-D3 can impact the transcription factors controlling the maturation by upregulating some differentiation gene in both granulocytes and monocytes linages and confirmed that the correlation between the markers and the regulatory transcription factors in response to ATRA and VIT-D3, which mimics the physiological pathway regulating maturation process. |
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Supervisor |
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Dr. Hadeel Sadoun Alsadoun |
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Thesis Type |
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Master Thesis |
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Publishing Year |
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1443 AH
2022 AD |
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Added Date |
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Saturday, January 28, 2023 |
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Researchers
| نهى عبدالله العمودي | Alamoudi, Noha Abdullah | Researcher | Master | |
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