Multi-Omics Investigation to on the Effect of Replication Stress on Leukemia Cells
Name
Vermeulen-sidneyv-meng-eecs-2022-thesis.pdf
Description
Thesis PDF
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16.81 MB
Format
Adobe PDF
Checksum (MD5)
acbba31e222907b3d0058043f8bc8f0f
Author(s)
Vermeulen, Sidney
Advisor(s)
Heiden, Matthew Vander
Date Issued
May 2022
Publisher
Massachusetts Institute of Technology
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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