Journal article
Evidence for Increased Response to Induced Endoplasmic Reticulum Stress in Myeloid Cells in Acquired Aplastic Anemia
Journal of pediatric hematology/oncology, Vol.39(3), pp.E163-E166
04/01/2017
DOI: 10.1097/MPH.0000000000000810
PMID: 28333839
Abstract
Autoimmune response targeting the hematopoietic stem cells highlights the current understanding of acquired aplastic anemia (AAA) pathogenesis. Upregulation of the unfolded protein response is the cell's rejoinder to a variety of stresses, which either result in restoring homeostasis or cell death by increased expression of the transcription factor C/EBP homologous protein. We hypothesized that there is an inherent increased sensitivity to various cellular stressors, including the ones that target endoplasmic reticulum (ER) in AAA leading to a decreased proliferation and potentially contributing to susceptibility to autologous cytotoxicity. Using archived bone marrow aspirate samples, we demonstrate that the culture-expanded AAA myeloid cells have an increased response to ER stress induced by tunicamycin leading to decreased cell proliferation. Within the AAA myeloid samples, we show that the disease status, active versus response to therapy at the time of sampling does not alter the ER stress response. This is the first report, which provides evidence for an inherent defective stress control in the myeloid cells as a possible mechanism of evolution of the disease process in AAA.
Details
- Title: Subtitle
- Evidence for Increased Response to Induced Endoplasmic Reticulum Stress in Myeloid Cells in Acquired Aplastic Anemia
- Creators
- Alpa Sidhu - Wayne State UniversityMichael U. Callaghan - Wayne State UniversityManisha S. Gadgeel - Wayne State UniversitySteven A. Buck - Wayne State UniversityAndrew M. Fribley - Wayne State UniversitySureyya Savasan - Children's Hospital of Michigan
- Resource Type
- Journal article
- Publication Details
- Journal of pediatric hematology/oncology, Vol.39(3), pp.E163-E166
- Publisher
- Lippincott Williams & Wilkins
- DOI
- 10.1097/MPH.0000000000000810
- PMID
- 28333839
- ISSN
- 1077-4114
- eISSN
- 1536-3678
- Number of pages
- 4
- Grant note
- Children's Research Center of Michigan Wayne State University Fund for Medical Research
- Language
- English
- Date published
- 04/01/2017
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984354499202771
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