Abstract

Aquaglyceroporin 9 (AQP9) is considered to be involved in numerous types of carcinogenic processes, particularly in liver carcinoma. AQP9 expression is significantly decreased in the human hepatocellular carcinoma when compared with the non-tumourigenic liver, which leads to increased resistance to apoptosis. In addition, AQP9 is permeable to glycerol and urea. The involvement of AQP9 in leukemia has not been fully delineated. It is proposed that abnormal proliferation of hematopoietic stem cells (HSCs) contributes to leukemia carcinogenesis. Therefore, the present study aimed to investigate the possible roles of AQP9 in HSCs and its effect on the intracellular glycerol content. HSCs and non-HSCs (nHSCs) were isolated via magnetic-activated cell sorting and then subjected to flow cytometry for evaluation of purity. White blood cells (WBCs) were isolated from peripheral blood from healthy volunteers. Furthermore, AQP9 expression was examined at the mRNA and protein levels using western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The glycerol content of HSCs, nHSCs and WBCs was evaluated by ELISA. Finally, in order to observe the morphology of HSCs and nHSCs, a blood smear was conducted and the cells were observed with Wright-Giemsa staining. The results indicated that the glycerol content in the HSCs was markedly greater than that in the nHSCs. AQP9 mRNA and protein expression was not detected in the HSCs and nHSCs, but was identified in the WBCs. Moreover, the HSC morphological characteristics included round or oval cells with round, slightly oval or irregularly shaped nuclei. Additionally, the nuclei occupied almost the entire cell, were located in the middle or were biased toward one side, and were stained light purple or red. Overall, our results indicated that intracellular glycerol is involved in HSC proliferation, despite the fact that glycerol is not mediated by AQP9. Hence, our findings may be useful in further understanding the mechanism of leukemia carcinogenesis, and these data may be valuable in developing future therapeutic strategies.

Highlights

  • Leukemia is one of the leading causes of death among patients suffering from malignant hematological disorders [1]

  • Aquaglyceroporin 9 (AQP9) is widely expressed in a number of tissues which are permeable to water, glycerol and urea

  • AQP9 is involved in the glycerol uptake by hepatocyte for gluconeogenesis [14]

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Summary

Introduction

Leukemia is one of the leading causes of death among patients suffering from malignant hematological disorders [1]. Despite the fact that great advances have been made in the treatment of leukemia, the overall survival rate has not greatly elevated [1,2]. The understanding of the mechanism by which neoplastic cells proliferate in leukemia is of great importance. It is known that alternation between the processes of dormancy and proliferation is very common in the human body, such as during wound healing, liver tissue regeneration and inflammatory proliferation [3,4,5]. Mucosal epithelium in the respiratory tract, the digestive tract and the genital ducts is in a dynamic division process [6]. Initiation of the abovementioned processes is based on the proliferation of original cells that possess stem cell properties. All of the aforementioned processes must occur under precise control, otherwise neoplasms may occur

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