000007620 001__ 7620
000007620 005__ 20240124114247.0
000007620 0247_ $$2DOI$$a10.6083/m4610zvt
000007620 037__ $$aETD
000007620 245__ $$aRegulation and signaling mechanisms of ror1 in b cell acute lymphoblastic leukemia
000007620 260__ $$bOregon Health and Science University
000007620 269__ $$a2017
000007620 336__ $$aThesis
000007620 502__ $$bPh.D.
000007620 520__ $$aAcute lymphocytic leukemia (ALL) is the most common cancer diagnosed in children and adolescents. Despite improved patient survival over the past fifty years, up to 20% of patients do not respond to therapy or develop resistance to treatment. Therefore, it is critical to identify new therapeutic targets to improve patient outcome. Approximately 4% of patients who present with ALL harbor a translocation between chromosomes 1 and 19 (t(1;19) pre-B-ALL). This translocation generates the TCF3-PBX1 fusion gene product, which arrests normal B cells in an immature developmental stage and maintains constitutively active kinase signaling. Small molecule tyrosine kinase inhibitors, like dasatinib, suppress these signaling pathways, but some leukemic cells can survive by activating rescue mechanisms. In response to dasatinib, the t(1;19) pre-B-ALL subtype exhibits upregulated ROR1 expression as an alternate mechanism to bypass kinase inhibition. ROR1 is required for t(1;19) pre-B-ALL survival, yet it cannot be easily targeted because ROR1 lacks kinase activity. Therefore, I sought to identify mechanisms important for ROR1 expression or signaling to determine additional proteins that may act as surrogate drug targets to inhibit ROR1.
000007620 650__ $$aSignal Transduction $$028380
000007620 650__ $$aProtein Kinases$$024752
000007620 650__ $$aRNA$$025527
000007620 650__ $$aLeukemia  $$021430
000007620 6531_ $$asmall interfering
000007620 691__ $$aSchool of Medicine$$041369
000007620 7001_ $$aChow, Marilynn
000007620 8564_ $$99b6cf625-f68f-4386-bf6b-72db54906984$$s2987588$$uhttps://digitalcollections.ohsu.edu/record/7620/files/Chow.Marilynn.2017.pdf
000007620 905__ $$a/rest/prod/zg/64/tm/50/zg64tm505
000007620 909CO $$ooai:digitalcollections.ohsu.edu:7620$$pstudent-work
000007620 980__ $$aTheses and Dissertations