Abstract

Objectives: Calreticulin (CALR) and CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) are two important multifunctional proteins which play different roles in regulation of hematopoiesis. Expressional changes of these genes were related to the malignancy.
 Methods: The present study aimed to investigate the expression levels of CALR and CEBPA genes in 96 de novo AML patients compared to 18 normal people as the control group through the Real-Time-PCR.
 Results: Results of the present study revealed that the expression of these genes was significantly higher in patients with AML than the normal group (P <0.0001). Furthermore, there was a significant and positive correlation between CALR and CEBPA (P= 0.001 and r= 0.348).
 Discussion: Higher level of CALR expression was expected, but the overexpression of CEBPA was on the contrary to its well-known role in the myeloid maturation. Based on the studies, CALR probably played roles in the expression of oncogenic CEBPA and it repressed the CEBPA translation in tumor suppressor gene (TSG).
 Conclusion: The present study first indicated the over-expression of CALR in AML patients and compared it with the healthy normal control group and also found a positive relationship between CALR and CEBPA expression in the AML patients.
 Bangladesh Journal of Medical Science Vol.19(4) 2020 p.730-736

Highlights

  • Calreticulin (CALR) is a multifunctional protein which is involved in regulation of intracellular calcium homoeostasis, protein synthesis, and cell adhesion and plays role as a chaperone[1, 2] .CALR contributes to the development of cancer through multiple paths and it can lead to the increased expression, migration and survival of cancer cells

  • Since the CALR and CCAAT enhancer binding protein alpha (CEBPA) are involved in the leukemogenesis, and the relationship between these genes is obvious at the protein level, the present study evaluated the correlation of these genes at the mRNA level in the Acute myeloid leukemia (AML) patients and its subgroups

  • Patients were divided into three groups; and the patients at the CALR expression level were put at the normal range (11 out of 96 AML patients) and had an intermediate expression level while those with levels above 5.46 to 240.471 (72 out of 96 patients) were considered as the patients with high expression; and those with levels under 1.30 to 0.0269 (13 out of 96 patients) were considered as the patients with low expression

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Summary

Introduction

Calreticulin (CALR) is a multifunctional protein which is involved in regulation of intracellular calcium homoeostasis, protein synthesis, and cell adhesion and plays role as a chaperone[1, 2] .CALR contributes to the development of cancer through multiple paths and it can lead to the increased expression, migration and survival of cancer cells. Over-expression of this gene can be seen in multitude of solid tumors and it is associated with more advanced and aggressive diseases[1,2,3,4] The mutation of this gene was seen in 15-25 percent of ET and MPL patients, but there was not any other common mutation such as JAK25. 17,18 According to the in-vitro studies, translation of CEBPA mRNA can be blocked by CALR binding. In this regard, CEBPA can be translated by mutation or deletion in the rich-GC site of CALR. Since the CALR and CEBPA are involved in the leukemogenesis, and the relationship between these genes is obvious at the protein level, the present study evaluated the correlation of these genes at the mRNA level in the AML patients and its subgroups

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