000000728 001__ 728
000000728 005__ 20260114141348.0
000000728 0247_ $$2DOI$$a10.6083/M4J964CR
000000728 037__ $$aETD
000000728 245__ $$aROR1 expression and function in B-cell malignancies
000000728 260__ $$bOregon Health and Science University
000000728 269__ $$a2011
000000728 336__ $$aDissertation
000000728 502__ $$bPh.D.
000000728 502__ $$gCell & Developmental Biology (sunsetting)
000000728 520__ $$aAberrant tyrosine kinase activity drives the development of many leukemias. To identify viability‑dependent kinases in acute lymphoblastic leukemia (ALL), we applied an RNAi‑assisted protein target identification (RAPID) assay across cytogenetic subtypes. In t(1;19) pediatric ALL, which produces the E2A‑PBX1 fusion, we identified the receptor tyrosine kinase ROR1 as uniquely essential for cell survival. We also found that t(1;19) ALL cells are highly sensitive to the kinase inhibitor dasatinib, which targets key mediators of pre‑B‑cell receptor (pre‑BCR) signaling. ROR1 and the pre‑BCR activate compensatory pathways, suggesting that dual‑pathway inhibition may offer an optimized therapeutic strategy.
000000728 540__ $$fCC BY
000000728 542__ $$fIn copyright - single owner
000000728 650__ $$aProtein Kinase Inhibitors$$035962
000000728 650__ $$aB-Lymphocytes$$015306
000000728 650__ $$aCell Differentiation$$016279
000000728 650__ $$aReceptor Tyrosine Kinase-like Orphan Receptors$$038804
000000728 650__ $$aSignal Transduction$$028380
000000728 650__ $$aPrecursor Cell Lymphoblastic Leukemia-Lymphoma$$037720
000000728 650__ $$aPre-B Cell Receptors$$037833
000000728 650__ $$aProtein-Tyrosine Kinases$$024762
000000728 650__ $$aRNA Interference$$034586
000000728 650__ $$aTyrosine Protein Kinase Inhibitors$$013842
000000728 650__ $$aReceptor Tyrosine Kinase-like Orphan Receptors$$038804
000000728 650__ $$aLeukemia, Lymphocytic, Chronic, B-Cell$$028421
000000728 6531_ $$acellular signal transduction
000000728 6531_ $$acellular control mechanisms
000000728 691__ $$aSchool of Medicine$$041369
000000728 692__ $$aDepartment of Cell, Developmental and Cancer Biology$$041399
000000728 7001_ $$aBicocca, Vincent$$uOregon Health and Science University$$041354
000000728 7201_ $$aDruker, Brian$$uOregon Health and Science University$$041354$$7Personal$$eAdvisor$$eMentor
000000728 8564_ $$907507fac-af7b-418e-9627-1f80ae5251db$$s3393514$$uhttps://digitalcollections.ohsu.edu/record/728/files/731_etd.pdf$$ePublic$$2522d872fc294d3f9fc227bf3e9163d47$$31
000000728 905__ $$a/rest/prod/4m/90/dv/51/4m90dv511
000000728 909CO $$ooai:digitalcollections.ohsu.edu:728$$pstudent-work
000000728 980__ $$aTheses and Dissertations