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Seminario biomol Maria Camila Ortega .pdf
- 1. MARIA CAMILA ORTEGA GONZÁLEZ 3RD SEMESTER MOLECULAR BIOLOGY
- 2. Acute lymphoblastic leukemia (ALL), including B-cell lymphoblastic leukemia (B-ALL) and T-cell lymphoblastic leukemia (T-ALL), is a heterogeneous blood and bone marrow disease characterized by malignant clones of primitive and immature lymphocytes that is frequently found in pediactric fields. ACUTE LIMPHOBLASTIC LEUKEMIA
- 3. Dexamethasone is a glucocorticoid often used alongside chemotherapy for ALL treatment. The dysregulated paraoxonase 2 (PON2) is a group of genes associated with cell invasion, metastasis, drug resistance (glucocorticoids), tumor therapy, and leads to a very poor prognosis regarding ALL. Silencing PON2 decreased the sensitivity of DEX-resistant ALL cells, improving its therapeutic effects. DEXAMETHASONE AND PON2
- 4. The high frequency of chemotherapy resistance is ultimately responsible for clinical relapse in acute lymphoblastic leukemia (ALL). Nevertheless, the molecular mechanism relevant to glucocorticoid (GC) resistance remains ambiguous. OBJECTIVE
- 5. METHODS SHRNA TRANSFECTION Transfection is used to silence a specific gene, in this case it was used to transfect the short hairpin RNA ofPON2 looking to silence this gene expression in REH and SUP-15R cells, creating a knockdown APOPTOSIS ASSAY Apoptosis assay was used to measure the apoptosis rate ofDEX resistant ALL cells after silencing PON2.
- 6. qRT-PCR WESTERN BLOTTING PCR is a test used to make millions of copies of a specific DNA and amplify them to facilitate the study. In this case it was used to find the mRNA levels of PON2 in different types of ALL (dex resistan, dex sensitive), to evaluate transfection efficiency and the expression of apoptosis proteins. Electrophoresis is used to separate the proteins so they can be specifically identified using an antibody. In this case, western blotting was performed for PON2, Bcl-2, Bax and GAPDH (used as an internal reference).
- 7. RESULTS PON2 is elevated in DEX-resistant ALL cells Silencing PON2 raises the DEX sensitivity of ALL cells PON2 silencing restores the sensitivity of ALL cell toward DEX-induced apoptosis
- 8. RESULTS PON2 knockdown inhibits tumor growth by sensitizing B-ALL cells to DEX in vivo
- 9. DISCUSSION AUTHOR STATEMENT STATUS Bachetti T, Ferretti G, Sahekbar A Agree Cellular resistance to GC has become a major obstacle in reaching successful treatment and prognosis for B-ALL Upregulation of PON2 has been observed in cancer, and it has been proposed that PON2 is implicated in stress resistance and tumor survival Poulard C, Baulu E, Lee BH Agree PON2 has been found to be highly upregulated in gene expression profiling studies addressing pediatric ALL Ross ME, Zhou X, Song G Agree
- 10. Understanding the reason treatments don´t work (incluiding genes being overexpressed/underexpressed) by conducting a series of experiments, will lead us to a more accurate diagnosis and treatment focused not only on the disease but the specifical condition. CONCLUSIONS The inhibition of PON2 can definitely improve the prognosis of patients struggling with ALL, this could only be known by going from the root of the disease to the bigger symptoms.
- 11. PON2 blockade overcomes dexamethasone resistance in acute lymphoblastic leukemia Dexamethasone PON2 ALL Dexamethasone is a glucocorticoid used in ALL treatment, if a patient is resistant to dexamethasone their prognosis won’t be as good PON2 is the group of genes related to dexamethasone resistance Acute lymphoblastic leukemia is a type ofcancer that affects the blood and bone marrow, causing the expression of immature lymphocytes Gets treated with Is very common in child Resistance When inhibited improves prognosis It works by inducing apoptosis By restoring the sensitivity to DEX