A Potential Target for Treating Acute Myeloid Leukemia: XBP1 involved in Endoplasmic Reticulum Stress
Nezahat Ece BIBEROĞLU1,Şeyma PUNAR1,Sema Sırma EKMEKÇI1,Muhlis Cem AR2,Ayşegül ÜNÜVAR3,Zeliha EMRENCE1,Tuğrul ELVERDI2,Ayşe SALIHOĞLU2,Zeynep KARAKAŞ3,Neslihan ABACI1
1Department of Genetics, İstanbul University, Aziz Sancar Institute of Experimental Medicine, İstanbul-Türkiye
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).

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.

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.

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. Keywords : Acute myeloid leukemia; binding immunoglobulin protein; cancer; endoplasmic reticulum stress; X-box protein 1