000042697 001__ 42697 000042697 005__ 20240226074224.0 000042697 0247_ $$2doi$$a10.6083/bpxhc42697 000042697 037__ $$aETD 000042697 041__ $$aeng 000042697 245__ $$aInvestigating transcriptional dysregulation in acute myeloid leukemia to inform novel therapeutic strategies 000042697 260__ $$bOregon Health and Science University 000042697 269__ $$a2024-02-23 000042697 336__ $$aDissertation 000042697 502__ $$bPh.D. 000042697 502__ $$gBiomedical Engineering 000042697 520__ $$aGene transcription is fundamental in establishing and maintaining cell identity and function. All normal cells are encoded with the same DNA, so transcription is essential for regulating many biological processes, including blood cell formation. Dysregulation of the complex transcriptional mechanisms governing blood cell formation can result in the development of hematologic malignancies, including acute myeloid leukemia (AML). AML is an aggressive blood cancer characterized by the rapid outgrowth of immature blood cells. Despite advances in treatment, AML remains an often fatal disease with a 5-year survival rate of less than 30%. This dissertation aims to uncover mechanisms of transcriptional dysregulation in AML, nominating novel molecular targets that can be used to design more effective treatment strategies. 000042697 540__ $$fCC BY 000042697 542__ $$fIn copyright - other owner 000042697 650__ $$aTranscription, Genetic$$027256 000042697 650__ $$aLeukemia, Myeloid, Acute$$028432 000042697 650__ $$aDrug Combinations$$018066 000042697 650__ $$aComputational Biology$$031511 000042697 650__ $$aDrug Resistance$$018079 000042697 650__ $$aGene Regulatory Networks$$037326 000042697 6531_ $$aFLT3-ITD 000042697 6531_ $$aLSD1 inhibition 000042697 6531_ $$aMYC blood super-enhancer 000042697 6531_ $$aGoPeaks 000042697 6531_ $$apriori 000042697 6531_ $$atranscription factor activity 000042697 6531_ $$aCUT&Tag 000042697 6531_ $$ahistone modification 000042697 6531_ $$avenetoclax resistance 000042697 691__ $$aSchool of Medicine$$041369 000042697 692__ $$aDepartment of Biomedical Engineering$$041397 000042697 7001_ $$aYashar, William$$uOregon Health and Science University$$041354$$10000-0002-8850-9850 000042697 789__ $$eCites$$wDOI: 10.1158/1541-7786.MCR-22-0745$$2DOI 000042697 789__ $$eCites$$wDOI: 10.1186/s13059-022-02707-w$$2DOI 000042697 789__ $$eCites$$wDOI: 10.1016/j.isci.2024.109124$$2DOI 000042697 789__ $$eIs new version of$$wDOI: 10.1182/blood-2023-175057$$2DOI 000042697 792__ $$a1. Yashar WM, Curtiss BM, Coleman DJ, VanCampen J, Kong G, Macaraeg J, Estabrook J, Demir E, Long N, Bottomly D, McWeeney SK, Tyner JW, Druker BJ, Maxson JE, Braun TP. Disruption of the MYC Superenhancer Complex by Dual Targeting of FLT3 and LSD1 in Acute Myeloid Leukemia. Mol Cancer Res. 2023 Jul 5;21(7):631-647. doi: 10.1158/1541-7786.MCR-22-0745. PMID: 36976323; PMCID: PMC10330306. </br> </br> 2. Yashar WM, Kong G, VanCampen J, Curtiss BM, Coleman DJ, Carbone L, Yardimci GG, Maxson JE, Braun TP. GoPeaks: histone modification peak calling for CUT&Tag. Genome Biol. 2022 Jul 4;23(1):144. doi: 10.1186/s13059-022-02707-w. PMID: 35788238; PMCID: PMC9252088. </br> </br> 3. Yashar WM, Estabrook J, Holly HD, Somers J, Nikolova O, Babur O, Braun TP, Demir E. Predicting transcription factor activity using prior biological information. iScience 2024 Feb 5. doi: 10.1016/j.isci.2024.109124. </br> </br> 4. YYashar WM, Pacentine IV, Tsuchiya M, Macaraeg J, Taherinasab A, Evans-Dutson S, O’Connell B, Lusardi T, Szczepanski N, Yardimci GG, Adey AC, Maxson JE, Braun TP. Differentiation State Plasticity as a Mechanism of BCL2 Inhibitor Resistance in Acute Myeloid Leukemia. Blood, 2023 November 28. doi: 10.1182/blood-2023-175057. 000042697 8564_ $$yWilliam Yashar Dissertation$$9724ec7fd-c807-491c-8950-19ab00caad3e$$s66893423$$uhttps://digitalcollections.ohsu.edu/record/42697/files/William.Yashar.2024.pdf 000042697 909CO $$ooai:digitalcollections.ohsu.edu:42697$$pstudent-work 000042697 980__ $$aTheses and Dissertations 000042697 981__ $$aPublished$$b2024-02-22