Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL

Synthesis, folding, and structural maturation of proteins occur in the endoplasmic reticulum (ER). Accumulation of misfolded or unfolded proteins in the ER lumen contributes to the induction of ER stress and activation of the unfolded protein response (UPR) signaling pathway. Under ER stress, the UPR tries to maintain cellular homeostasis through different pathways, including the inositol-requiring enzyme 1 alpha (IRE1α)-dependent ones. IRE1α is located in an ER membrane, and it is evolutionarily the oldest UPR sensor. Activation of IRE1α via ER stress triggers the formation of the spliced form of XBP1 (XBP1s), which has been linked to a pro-survival effect in cancer cells. The role of IRE1α is critical for blood cancer cells, and it was found that the levels of IRE1α and XBP1s are elevated in various hematological malignancies. This review paper is focused on summarizing the latest knowledge about the role of IRE1α and on the assessment of the potential utility of IRE1α inhibitors in blood cancers.

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IRE1α Inhibitors as a Promising Therapeutic Strategy in Blood Malignancies

Wiese

Siwecka

Wawrzynkiewicz

et al. 2022

Cancers

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The role of gene expression hypoxia-inducible factor-1a and serum level monocyte chemoattractant protein-1 in the incidence of chronic myeloid leukemia in Iraqi patients

Naeem,

Alsaadi

2024

Iraqi Journal of Hematology

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BACKGROUND: Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy described by a translocation between chromosomes 9 and 22. There are many factors genetic or nongenetic effect on disease progression such as growth factors and transcription factors act as oncogenes or tumor suppressor genes. OBJECTIVES: The purpose of this research was to investigate the role of hypoxia-inducible factor (HIF1A) gene expression with CML, as well as the role of monocyte chemoattractant protein-1 (MCP-1) as a predictive biomarker on disease progression. MATERIALS AND METHODS: The current study consists of three groups: first group includes 50 newly diagnosed CML patients (females 22 and males 28), second group consists of 50 CML patients treated with tyrosine kinase inhibitor (TKI) with a complete molecular response (p210 BCR-ABL transcript levels ≤0.1% IS) (female 25 and male 25), and third group included another 50 apparently healthy volunteers (female 20 and male 30). The patients were admitted from the National Center of Hematology/Mustansiriyah University. All patients are diagnosed according to a complete blood count (CBC), a bone marrow examination, and a BCR-ABL gene test. RESULTS: Reverse transcription-quantitative polymerase chain reaction was applied to assess the expression levels of the HIF-1A gene and serum level of MCP1 by enzyme-linked immunosorbent assay. The results displayed downregulated of the HIF1A gene messenger RNA in CML patients in comparison to the controls group, as well as no statistically significant link was discovered when the fold of expression was correlated with the age and gender of CML patients. CONCLUSION: HIF1-alpha gene has an important role in pathological pathways such as angiogenesis. According to this study, HIF1-alpha gene is not an appropriate prognostic biomarker for detecting the risk of CML as well as MCP1 is thought to be a predictor of CML progression.

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Triangle collaboration assessment of autophagy, ER stress and hypoxia in leukemogenesis: a bright perspective on the molecular recognition of B-ALL

Cited by 2 publications

References 30 publications

IRE1α Inhibitors as a Promising Therapeutic Strategy in Blood Malignancies

IRE1α Inhibitors as a Promising Therapeutic Strategy in Blood Malignancies

The role of gene expression hypoxia-inducible factor-1a and serum level monocyte chemoattractant protein-1 in the incidence of chronic myeloid leukemia in Iraqi patients

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