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Anticancer Agents Med Chem. 2019 Dec 10. doi: 10.2174/1871520619666191211101357. [Epub ahead of print]

Association of GRP78, HIF-1α and BAG3 Expression with the Severity of Chronic Lymphocytic Leukemia.

Author information

1
Faculty of Nursing and Midwifery, Golestan University of Medical Sciences, Shast Kola Road, Gorgan. Iran.
2
Department of Medical Veterinary, Azad University, Garmsar Branch, Garmsar. Iran.
3
Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical, Tehran. Iran.
4
Faculty of Medical Sciences, Tarbiat Modares University, Tehran. Iran.
5
Faculty of Hematology, School of Allied Health, Iran University of Medical Sciences, Tehran. Iran.
6
Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad. Iran.

Abstract

INTRODUCTION:

Parallel with the progression of Chronic Lymphocytic Leukemia (CLL), the levels of 78KDa Glucose-Regulated Protein (GRP78) and Hypoxia-Inducible Factor 1 alpha (HIF-1α) are increased as they may activate the induction of anti-apoptotic proteins such as BCL2 Associated Athanogene 3 (BAG3). Previous studies have indicated that there is a positive correlation among GRP78, HIF-1α and BAG3.

OBJECTIVE:

To evaluate the effect of metabolic factors involved in invasive CLL on apoptotic factors.

METHODS:

A case-control study was conducted on 77 patients diagnosed with CLL along with 100 healthy individuals. Cell blood count was performed for all participants. According to the Binet's classification, CLL patients were divided into different groups. B cells were isolated from peripheral blood of CLL patients by binding to anti-CD19 beads. The expression of BAG3, GRP78 and HIF-1α genes was analyzed using RT-PCR method. To confirm the results of RT-PCR, western blot analysis was carried out.

RESULTS:

The results showed that there was a strong association among the expression of BAG3, GRP78 and HIF-1α. The stage of CLL in patients was highly correlated with the expression rate of each gene (p<0.001). Accordingly, the western blot analysis indicated that the concentrations of GRP78 and HIF-1α were significantly higher than the expression of BAG3 considering the stage of CLL.

CONCLUSION:

It was shown that increased expression of GRP78 and HIF-1α could result in the elevation of BAG3, as well as the disease progression. Therefore, the role of these metabolic factors might be more pronounced compared with the anti-apoptotic agents to monitor disease progression in CLL patients.

KEYWORDS:

BAG3; CLL; GRP78; HIF-1α; RT-PCR; western blot

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