2Department of Internal Medicine, İstanbul University-Cerrahpaşa, Cerrahpaşa Faculty of Medicine, İstanbul-Türkiye
3Department of Pediatric Hematology and Oncology, Istanbul Faculty of Medicine, İstanbul-Türkiye DOI : 10.5505/tjo.2023.3968 OBJECTIVE
Endoplasmic reticulum (ER) stress, which occurs as a result of the accumulation of misfolded or unfolded proteins, has been observed in many cancers. To re-establish the ER homeostasis, pathways of unfolded protein response (UPR) are activated. The effect of ER stress-activated UPR pathways on leukemogenesis has not been elucidated. In this study, we aimed to find out whether activated UPR pathways were involved in acute myeloid leukemia (AML).
METHODS
Expression levels of the 2 UPR components, binding immunoglobulin protein (BiP), and X-box protein
1 (XBP1), as well as the HLA-B were analyzed in 100 newly diagnosed AML patients using quantitative
and qualitative polymerase chain reaction techniques.
RESULTS
Fifteen of the 100 newly diagnosed AML patients were shown to carry the spliced XBP1 (XBP1s) variant.
Furthermore, in patients with acute promyelocytic leukemia (APL), a subtype of AML, expression levels of
XBP1, and BiP were significantly higher than in non-APL patients (p<0.001 and p<0.015, respectively). It
was determined that 6 of 15 (40%) AML patients carrying XBP1s variant were positive for myeloperoxidase.
CONCLUSION
Our study provides adequate evidences for the involvement of activated UPR pathways in some of the
AML patients by showing the presence XBP1s variant and increased expression levels for XBP1 and BiP.
Thus, agents targeting XBP1s might serve as a new approach for anti-cancer therapy.