TSLP as a Potential Therapy for CRLF2 B-Cell Acute Lymphoblastic Leukemia

dc.contributor.advisorCasiano, Carlos A
dc.contributor.advisorFigueroa, Johnny
dc.contributor.advisorFrancis-Boyle, Olivia
dc.contributor.advisorSun, Richard
dc.contributor.advisorDovat, Sinisa
dc.contributor.authorAlkashgari, Hossam
dc.date.accessioned2023-06-14T06:40:02Z
dc.date.available2023-06-14T06:40:02Z
dc.date.issued2023
dc.description.abstractCytokine receptor-like factor 2 B-cell acute lymphoblastic leukemia (CRLF2 B- ALL) is a high-risk subtype characterized by CRLF2 overexpression with poor survival rates in children and adults. CRLF2 and interleukin-7 receptor alpha (IL-7Rα) form a receptor for the cytokine thymic stromal lymphopoietin (TSLP), which induces JAK/STAT and PI3K/AKT/mTOR pathway signals. Previous studies from our group showed that low TSLP doses increased STAT5, AKT, and S6 phosphorylation and contributed to CRLF2 B-ALL cell survival. Here we investigated the role of TSLP in the survival and proliferation of CRLF2 B-ALL cells in vitro and in vivo. We hypothesized that high doses of TSLP increase CRLF2 signals and contribute to increased proliferation of CRLF2 B-ALL cells in vitro and in vivo. Interestingly, we observed the opposite effect. Specifically, high doses of TSLP induced apoptosis in human CRLF2 B-ALL cell lines in vitro, prevented engraftment of CRLF2 B-ALL cells, and prolonged the survival of +TSLP patient-derived-xenograft mice. Mechanistically, we showed that continuous and one hour pulse high dose of TSLP induced loss of its receptor and loss of CRLF2 signals in vitro. These results suggest that high doses of TSLP could be further investigated as a potential therapy for the treatment of CRLF2 B-ALL.
dc.format.extent90
dc.identifier.urihttps://hdl.handle.net/20.500.14154/68374
dc.language.isoen_US
dc.subjectTSLP
dc.subjectCRLF2
dc.subjectB-ALL
dc.subjectIL-7Rα
dc.subjectSOCS
dc.subjectapoptosis
dc.subjectPDX
dc.subjectSTAT5
dc.subjectS6
dc.titleTSLP as a Potential Therapy for CRLF2 B-Cell Acute Lymphoblastic Leukemia
dc.typeThesis
sdl.degree.departmentDepartment of Basic Sciences
sdl.degree.disciplinePhysiology
sdl.degree.grantorLoma Linda University
sdl.degree.nameDoctor of Philosophy

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