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Turkish Journal of Medical Sciences

Abstract

Background/aim: The protein kinase RNA-like endoplasmic reticulum kinase (PERK) pathway plays a critical role in preventing the accumulation of misfolded or unfolded proteins within the endoplasmic reticulum. In this study, the role of the PERK signaling pathway was evaluated in newly diagnosed, treatment-naïve patients with acute myeloid leukemia (AML).

Materials and methods: Plasma levels of eukaryotic translation initiation factor 2-alpha kinase 3 (eIF2AK3), glucose-regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), CCAAT/enhancer-binding protein homologous protein (CHOP), hypoxia-inducible factor-1 alpha (HIF-1α), and caspase 3 were measured by enzyme-linked immunosorbent assay in peripheral blood samples obtained from AML patients and healthy controls.

Results: A total of 40 individuals were included, comprising 19 (47%) AML patients and 21 (53%) healthy controls. HIF-1α, eIF2AK3, GRP78, ATF6, CHOP, and caspase 3 levels were significantly higher in the AML group than in the control group (p = 0.019, 0.005, <0.001, 0.006, <0.001, and <0.001, respectively). No significant differences were observed in HIF-1α, GRP78, ATF6, CHOP, and caspase 3 levels between diagnosis and the 30th day of remission-induction therapy in the AML group, whereas a significant decrease was observed in eIF2AK3 levels (p = 0.049). At diagnosis, a strong positive correlation was found between GRP78 and CHOP levels (r = 0.740, p < 0.001), and a moderate positive correlation was detected between CHOP and caspase 3 levels (r = 0.514, p = 0.024) in the AML group. In the Cox regression analysis of the AML cohort, no statistically significant association was identified between overall survival and age, risk category, or biomarker levels (HIF-1α, eIF2AK3, GRP78, ATF6, CHOP, and caspase 3).

Conclusion: PERK and ATF6 signaling pathways were activated in patients with AML. Targeting the unfolded protein response pathway may represent a promising therapeutic strategy for patients with AML.

Author ORCID Identifier

NERGİZ ERKUT: 0000-0002-6683-0432

TURHAN KÖKSAL: 0009-0002-7955-2838

SELİM DEMİR: 0000-0002-1863-6280

AHMET MENTEŞE: 0000-0003-2036-5317

ÖZLEN BALTA: 0000-0002-2670-022X

MEHMET SÖNMEZ: 0000-0002-2176-4371

DOI

10.55730/1300-0144.6168

Keywords

ATF6 signaling pathway, Endoplasmic reticulum stress, hypoxia, apoptosis, PERK signaling pathway

First Page

344

Last Page

350

Publisher

The Scientific and Technological Research Council of Türkiye (TÜBİTAK)

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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