Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


G_Zimmerman_MS_Thesis_OL_upload.pdf (775.4 KB)

ETD Abstract Container

Abstract Header

T-ALL LEUKEMIA DYSREGULATES STROMAL BONE MARROW ENVIRONMENT AND DISRUPTS NICHE-STEM CELL SIGNALING AXIS

Zimmerman, Grant Robert
http://rave.ohiolink.edu/etdc/view?acc_num=case1436293859

Abstract Details

2015, Master of Sciences, Case Western Reserve University, Pathology.
Recent characterization of the bone marrow microenvironment has pointed to comprehensive dysregulation of hematopoietic-stromal interactions in the context of leukemia. We used common oncogenic mutations in Notch to probe these dysregulated interactions. We found an upregulation in cellular homing receptor CXCR4 in Notch-driven leukemic cells. Inhibition of Notch signaling using a gamma-secretase inhibitor in the stromal environment led to lessening of leukemic burden, relief of stem cell suppression, and normalized expression of CXCR4 by non-leukemic hematopoietic progenitor cells. The stromal environment was further characterized. Leukemic dysregulation was seen to increase stromal expression of adhesion molecules while decreasing osteoblastic differentiation. Final experiments sought to tie these observations together using imaging to characterize differences in cellular homing based on leukemic subpopulations expressing different levels of CXCR4. Leukemic cells expressing high levels of CXCR4 were seen to migrate preferentially to vascular structures, suggesting a propensity to more proliferative bone marrow microenvironments.
Lan Zhou, MD/PhD (Advisor)
Diana Ramirez-Bergeron, PhD (Committee Chair)
32 p.
Medicine; Molecular Biology; Pathology
Bone Marrow; Stromal Cells; Acute Lymphoblastic Leukemia; T-ALL; CXCR4; Notch; Leukemic Stem Cell

Recommended Citations

Citations

  • Zimmerman, G. R. (2015). T-ALL LEUKEMIA DYSREGULATES STROMAL BONE MARROW ENVIRONMENT AND DISRUPTS NICHE-STEM CELL SIGNALING AXIS [Master's thesis, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1436293859

    APA Style (7th edition)

  • Zimmerman, Grant. T-ALL LEUKEMIA DYSREGULATES STROMAL BONE MARROW ENVIRONMENT AND DISRUPTS NICHE-STEM CELL SIGNALING AXIS. 2015. Case Western Reserve University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1436293859.

    MLA Style (8th edition)

  • Zimmerman, Grant. "T-ALL LEUKEMIA DYSREGULATES STROMAL BONE MARROW ENVIRONMENT AND DISRUPTS NICHE-STEM CELL SIGNALING AXIS." Master's thesis, Case Western Reserve University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1436293859

    Chicago Manual of Style (17th edition)

case1436293859
445
© 2015, some rights reserved.Creative Commons License T-ALL LEUKEMIA DYSREGULATES STROMAL BONE MARROW ENVIRONMENT AND DISRUPTS NICHE-STEM CELL SIGNALING AXIS by Grant Robert Zimmerman is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.