Local Renin-Angiotensin System in Normal Hematopoietic and Multiple Myeloma-Related Progenitor Cells

Uz, Burak; Tatonyan, Suzin Catal; Sayitoğlu, Müge; Erbilgin, Yücel; Hatırnaz, Özden; Aksu, Salih; Büyükaşık, Yahya; Sayınalp, Nilgün; Göker, Hakan; Özcebe, Osman; Özbek, Uğur; Haznedaroğlu, İbrahim C.

doi:10.4274/tjh.2013.0011

Cited by 7 publications

(4 citation statements)

References 45 publications

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“…Moreover, there are limited data showing RBP-J gene mutations in leukemia patients [24,25]. Serum ACE was found increased in MM patients and local RAS components were also found in the following studies [26,27].…”

Section: Discussionmentioning

confidence: 99%

The Role of Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma

Saka

Sayitoğlu

Istemihan

et al. 2019

Tjh

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Objective: Angiotensin II promotes growth and angiogenesis via type 1 receptors (AGTR1) in certain tumors. In this study, we examine the bone marrow AGTR1 expression in multiple myeloma (MM) and its relationship with the regulation of angiogenesis and prognostic factors. Materials and Methods: Bone marrow AGTR1 mRNA levels of 39 MM patients and 15 healthy controls were analyzed with quantitative RT-PCR. Immunohistochemical staining of the tissue vascular endothelial growth factor (VEGF), CD34, and factor VIIIrAg (fVIIIrAg) was used to assess bone marrow angiogenesis. Results: Bone marrow samples of the patients showed increased VEGF, fVIIIrAg, and CD34 staining and higher AGTR1 expression levels when compared to controls. Patients with severe-diffuse bone marrow infiltration showed higher bone marrow VEGF, fVIIIrAg, CD34, and AGTR1 mRNA levels when compared to other patients. Conclusion: AGTR1 expression was found positively correlated with plasma β2-microglobulin level and patients with increased AGTR1 expression showed increased bone marrow CD34 levels.

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Section: Discussionmentioning

confidence: 99%

The Role of Local Bone Marrow Renin-Angiotensin System in Multiple Myeloma

Saka

Sayitoğlu

Istemihan

et al. 2019

Tjh

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“…The overall results of the present data mining study reveal the complicated nature of MM [28] and locate the drug bortezomib at the critical crossroads of the pathobiology of the disease, driving the clinical course of MM. For instance, the LP-1 cell line was found to be resistant to bortezomib in our present study (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Expression Profiles of the Individual Genes Corresponding to the Genes Generated by Cytotoxicity Experiments with Bortezomib in Multiple Myeloma

Ghasemi¹,

Alpsoy²,

Turk³

et al. 2016

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Objective:Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib.Materials and Methods:We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was “Robust Multi-array analysis” normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regression-based approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis.Results:Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways.Conclusion:The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

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“…We had initially indicated that there is a local hematopoietic bone marrow (BM) renin-angiotensin system (RAS), active in the physiological and pathological hematopoiesis (reviewed by Haznedaroglu and Beyazit [ 1 ]). Turkish Journal of Hematology has already published two critical research papers on the impact of the local BM RAS on the pathobiological course of neoplastic hematological disorders [ 2 , 3 ].…”

Section: To the Editormentioning

confidence: 99%