{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Das S"],"funding":["DBT/Wellcome Trust India Alliance","Wellcome Trust"],"pubmed_abstract":["Understanding clinically relevant driver mechanisms of acquired chemo-resistance is crucial for elucidating ways to circumvent resistance and improve survival in patients with acute myeloid leukemia (AML). A small fraction of leukemic cells that survive chemotherapy have a poised epigenetic state to tolerate chemotherapeutic insult. Further exposure to chemotherapy allows these drug persister cells to attain a fixed epigenetic state, which leads to altered gene expression, resulting in the proliferation of these drug-resistant populations and eventually relapse or refractory disease. Therefore, identifying epigenetic modulations that necessitate the survival of drug-resistant leukemic cells is critical. We detail a protocol to identify epigenetic modulators that mediate resistance to the nucleoside analog cytarabine (AraC) using pooled shRNA library screening in an acquired cytarabine-resistant AML cell line. The library consists of 5,485 shRNA constructs targeting 407 human epigenetic factors, which allows high-throughput epigenetic factor screening."],"journal":["Journal of visualized experiments : JoVE"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7614927"],"repository":["biostudies-literature"],"pubmed_title":["Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype."],"pmcid":["PMC7614927"],"funding_grant_id":["IA/S/17/1/503118"],"pubmed_authors":["Ijee S","Velayudhan SR","Das S","Stallon Illangeswaran RS","Balasubramanian P","Kumar S"],"additional_accession":[]},"is_claimable":false,"name":"Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype.","description":"Understanding clinically relevant driver mechanisms of acquired chemo-resistance is crucial for elucidating ways to circumvent resistance and improve survival in patients with acute myeloid leukemia (AML). A small fraction of leukemic cells that survive chemotherapy have a poised epigenetic state to tolerate chemotherapeutic insult. Further exposure to chemotherapy allows these drug persister cells to attain a fixed epigenetic state, which leads to altered gene expression, resulting in the proliferation of these drug-resistant populations and eventually relapse or refractory disease. Therefore, identifying epigenetic modulations that necessitate the survival of drug-resistant leukemic cells is critical. We detail a protocol to identify epigenetic modulators that mediate resistance to the nucleoside analog cytarabine (AraC) using pooled shRNA library screening in an acquired cytarabine-resistant AML cell line. The library consists of 5,485 shRNA constructs targeting 407 human epigenetic factors, which allows high-throughput epigenetic factor screening.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2025-04-25T20:06:02.492Z","creation":"2025-04-06T08:12:09.511Z"},"accession":"S-EPMC7614927","cross_references":{"pubmed":["35786700"],"doi":["10.3791/63383"]}}