Abstract

Objective: The prominent functions of the local renin-angiotensin system (RAS) in primitive hematopoiesis further support the hypothesis that local autocrine bone marrow RAS could also be active in neoplastic hematopoiesis. The aim of this study is to examine critical RAS elements in normal CD34+ hematopoietic stem cells and multiple myeloma (MM)-related progenitor cells.Materials and Methods: The study group comprised the total bone marrow cells (CBM) of 10 hematologically normal people, the CD34+ stem cell samples (CD34+CBM) of 9 healthy donors for allogeneic peripheral stem cell transplantation, and the CD34+ stem cell samples (CD34+MM) of 9 MM patients undergoing autologous peripheral stem cell transplantation. We searched for the gene expression of the major RAS components in healthy hematopoietic cells and myeloma cells by quantitative real-time polymerase chain reaction analysis.Results: RENIN, angiotensinogen (ANGTS), and angiotensin converting enzyme-I (ACE I) mRNA expression levels of CBM were significantly higher than those in myeloma patients (p=0.03, p=0.002, and p=0.0008, respectively). Moreover, RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01). However, ACE I expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89).Conclusion: Although found to be lower than in the CBM and CD34+CBM hematopoietic cells, the local RAS components were also expressed in CD34+MM hematopoietic cells. This point should be kept in mind while focusing on the immunobiology of MM and the processing of autologous cells during the formation of transplantation treatment protocols.

Highlights

  • The local hematopoietic renin-angiotensin system (RAS) affects the essential steps of hematopoiesis in the bone marrow (BM) microenvironment [1,2,3,4]

  • RENIN and ANGTS mRNA expression levels were significantly higher in CD34+ stem cell samples of healthy allogeneic donors compared to those in myeloma patients (p=0.001 and p=0.01)

  • anjiotensin dönüştürücü enzim-I (ACE I) expression levels were similar in CD34+CBM and CD34+MM hematopoietic cells (p=0.89)

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Summary

Introduction

The local hematopoietic renin-angiotensin system (RAS) affects the essential steps of hematopoiesis in the bone marrow (BM) microenvironment [1,2,3,4]. Myelopoiesis, erythropoiesis, thrombopoiesis, and other cellular lineages are influenced by the actions of the local BM RAS [3]. Besides those cellular effects, the local RAS [4,5] is active in the BM stromal niche for the crucial governing of hematopoietic functions [6,7]. The RAS affects numerous biological events that are important for the formation and function of blood cells. The prominent functions of the local RAS in primitive hematopoiesis further support the hypothesis that the local autocrine BM RAS could be active in neoplastic hematopoiesis [3]

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Conclusion

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