RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2 ‑deficient human acute myeloid leukemia.

RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2‑deficient human acute myeloid leukemia. Oncol Rep. 2020 Aug 10;: Authors: Xu Y, Lin Y, Luo Y, Yang Y, Long B, Fang Z, Liu L, Zhang J, Zhang X Abstract RAD52 (Radiation sensitive 52) is a key factor in DNA damage repair (DDR) bypass, which participates in single‑strand annealing (SSA) after DNA damage end excision, while breast cancer type 1 susceptibility protein (BRCA1)/breast cancer type 2 susceptibility protein (BRCA2) play critical roles in homologous recombination (HR) repair. The present study aimed to determine whether RAD52‑induced regulation of repair bypass occurs in acute myeloid leukemia (AML) cells and to explore the underlying mechanism. Herein, we applied an RAD52 aptamer to AML cells with downregulated BRCA1/2. RAD52 aptamer inhibited AML cell proliferation detected by cell counting, promoted cell apoptosis obtained by flow cytometry, and suppressed DNA damage repair behavior measured by comet assay and flow cytometry, after drug intervention during low expression of BRCA1/2. During this process, DDR‑related cell cycle checkpoint proteins were activated, and the cells were continuously arrested in the S/G2 phase, which affected the cell damage repair process. Concurrently, the expression levels of apoptosis‑related proteins were also altered. Furthermore, the expression of STAT3 and p‑STAT3 was downregulated by the RAD52 aptamer, suggesting that RAD52 affects th...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

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Abstract In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stim...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II Source Type: research
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Source: Blood - Category: Hematology Authors: Tags: 636. Myelodysplastic Syndromes-Basic and Translational Studies: Poster III Source Type: research
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Background: BRCA1 and BCRA2 (breast cancer 1 and 2) are tumor suppressor genes involved in repair of DNA double-strand breaks. Loss of BRCA1/2 activity by (germline) mutations (mut) or downregulation (DR) of gene expression (GE) correlates with an increased risk of breast and ovarian cancer. Mut in or reduced GE of BRCA1/2 have also been implicated in some hematological malignancies, although data are so far scarce. Moreover, PARP1 inhibitors, known to induce synthetic lethality in tumors harboring BRCA1/2 mut were shown to affect FLT3(ITD)-positive AML (acute myeloid leukemia) cells.Aims: Investigation of BRCA1/2 mut and ...
Source: Blood - Category: Hematology Authors: Tags: 603. Oncogenes and Tumor Suppressors: Poster I Source Type: research
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