Evidence for Increased Response to Induced Endoplasmic Reticulum Stress in Myeloid Cells in Acquired Aplastic Anemia.
J Pediatr Hematol Oncol
; 39(3): e163-e166, 2017 04.
Article
in En
| MEDLINE
| ID: mdl-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Myeloid Cells
/
Unfolded Protein Response
/
Endoplasmic Reticulum Stress
/
Anemia, Aplastic
Limits:
Humans
Language:
En
Journal:
J Pediatr Hematol Oncol
Journal subject:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Year:
2017
Type:
Article