Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells
Differentiation therapy has the potential to treat cancers like acute myeloid leukemia. While the DHODH inhibitor has been shown to induce differentiation in an AML model, the mechanism that this happens is still unknown. Here we characterize a similar differentiation phenotype in the CML cell line...
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| Other Authors: | |
| Format: | Thesis |
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Massachusetts Institute of Technology
2022
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| Online Access: | https://hdl.handle.net/1721.1/144682 |
| _version_ | 1826189635049488384 |
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| author | Vermeulen, Sidney |
| author2 | Heiden, Matthew Vander |
| author_facet | Heiden, Matthew Vander Vermeulen, Sidney |
| author_sort | Vermeulen, Sidney |
| collection | MIT |
| description | Differentiation therapy has the potential to treat cancers like acute myeloid leukemia. While the DHODH inhibitor has been shown to induce differentiation in an AML model, the mechanism that this happens is still unknown. Here we characterize a similar differentiation phenotype in the CML cell line K562. Like AML lines studied previously, replication stress leads cells to adopt a cell state similar to oncogene knockdown. Replication stress is likely not acting through chromatin state directly given that upregulated genes did not vary in their H3K27 modification or polymerase pausing, and many chromatin modifier genes that suppressed THP1 differentiation did not also suppress differentiation in K562s. Thus, the mechanism of how replication stress leads to differentiation is still unknown. |
| first_indexed | 2024-09-23T08:18:44Z |
| format | Thesis |
| id | mit-1721.1/144682 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:18:44Z |
| publishDate | 2022 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/1446822022-08-30T04:05:25Z Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells Vermeulen, Sidney Heiden, Matthew Vander Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Differentiation therapy has the potential to treat cancers like acute myeloid leukemia. While the DHODH inhibitor has been shown to induce differentiation in an AML model, the mechanism that this happens is still unknown. Here we characterize a similar differentiation phenotype in the CML cell line K562. Like AML lines studied previously, replication stress leads cells to adopt a cell state similar to oncogene knockdown. Replication stress is likely not acting through chromatin state directly given that upregulated genes did not vary in their H3K27 modification or polymerase pausing, and many chromatin modifier genes that suppressed THP1 differentiation did not also suppress differentiation in K562s. Thus, the mechanism of how replication stress leads to differentiation is still unknown. M.Eng. 2022-08-29T16:04:27Z 2022-08-29T16:04:27Z 2022-05 2022-05-27T16:18:28.297Z Thesis https://hdl.handle.net/1721.1/144682 In Copyright - Educational Use Permitted Copyright MIT http://rightsstatements.org/page/InC-EDU/1.0/ application/pdf Massachusetts Institute of Technology |
| spellingShingle | Vermeulen, Sidney Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title | Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title_full | Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title_fullStr | Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title_full_unstemmed | Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title_short | Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells |
| title_sort | multi omics investigation to on the effect of replication stress on leukemia cells |
| url | https://hdl.handle.net/1721.1/144682 |
| work_keys_str_mv | AT vermeulensidney multiomicsinvestigationtoontheeffectofreplicationstressonleukemiacells |