Oosthoek, Janna (2012) The influence of a hypoxic profile on the division in the three different vascular morphology groups in bone marrow biopsies of AML patients. thesis, Medicine.
Full text available on request.Abstract
Acute myeloid leukemia (AML), also known as blood cancer, is a disease in which malignant cells replace normal blood production. Bone marrow biopsies at diagnosis display heterogeneity in angiogenesis. Different vascular patterns can be distinguished in AML bone marrow biopsies. These vascular patterns were divided into three subgroups, based on number, size and pattern of the vessels. Accumulating evidence identified hypoxia and the key transcriptional system, HIF (hypoxia-inducible factor), as major triggers for angiogenesis. The goal of this research clerkship was, to determine if a hypoxic profile has influence on the division in the three different vascular morphology groups in bone marrow biopsies of AML patients, and if this is related with outcome. In a pilot study, a hypoxic profile was formed with three different biomarkers, using immunohistochemical staining for HIF-1a, HIF-2a, GLUT-1, CA IX, VEGFA and VEGFR2. After analysis together with a pathologist (dr. S. Rosati), we decided that the hypoxic profile would consist of GLUT-1, HIF-1a and HIF-2a. Bone marrow biopsies of AML patients at diagnosis (n=93) and normal bone marrow biopsies (n=10) were stained for this hypoxic profile. Expression of HIF-1a in the nucleus is associated with a significant lower probability of overall survival (P=0.027), but not with the different vascular morphology groups. The level of GLUT-1 expression had a significant effect (P=0.00) on the division in the vascular morphology groups. However, GLUT-1 was expressed on the whole erythroid lineage and not on the leukemic cells as we had expected. Patients with GLUT-1 levels above the median had a trend towards a longer overall survival. Immunohistochemistry of HIF-2a was to diffuse to evaluate. In conclusion, our data demonstrate activation of the HIF pathway in the bone marrow of AML patients and indicate that immunohistochemical expression of HIF-1a in the nucleus is associated with poor outcome.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | FaFaculty supervisor(s) and Bont, Eveline de MD PhD and Professor and Head division of pediatric oncology/hematology and Beatrix childrens hospital and University Medical Center Groningen and & and Elst, Arja ter PhD and Department of pediatric oncology/hematology and University Medical Center Groningen and culty supervisor and Eveline de Bont, MD PhD and Professor and Head division of pediatric oncology/hematology and Beatrix childrens hospital and University Medical Center Groningen and & and Arja ter Elst, PhD and Department of pediatric oncology/hematology and University Medical Center Groningen |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:00 |
| Last Modified: | 25 Jun 2020 11:00 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2027 |
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