Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

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

doi:10.1177/1470320312464677

Cited by 13 publications

(10 citation statements)

References 41 publications

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“…Drug tolerability, patient compliance of TKI, physician adherence to TKI, and off-target TKI complications should always be monitored during the CML treatment. Otherwise, late, off-target complications of TKI (lung toxicity, 35 cardiac toxicity, 36 , 37 metabolic syndrome 21 , bone toxicity, 38 arterial and venous occlusive events, 39 pancreas toxicity 1 , and others) may limit the benefits of the given TKI. Proper therapeutic interventions based on the therapeutic monitoring of the CML patients and TKI drugs are described in the ELN 2013 recommendations.…”

Section: Practical Problems In the Long-term Monitoring Of Tki Treatmmentioning

confidence: 99%

Monitoring the Response to Tyrosine Kinase Inhibitor (Tki) Treatment in Chronic Myeloid Leukemia (Cml)

Haznedaroğlu

2013

Mediterr J Hematol Infect Dis

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The aim of oral tyrosine kinase inhibitor (TKI) treatment in chronic myeloid leukemia (CML) is to get ideal hematological, cytogenetic, molecular responses at the critical time points. The depth of the response obtained with TKI and the time to achieve this response are both important in predicting the prognosis in patients with CML. The high efficacy of the TKI treatment of CML has prompted the need for accurate methods to monitor response at levels below the landmark of CCyR. Quantification of BCR-ABL transcripts has proven to be the most sensitive method available and has shown prognostic impact with regard to progression-free survival. European LeukemiaNet (ELN) molecular program harmonized the reporting of results according to the IS (International harmonization of Scale) in Europe. The aim of this review is to outline monitoring the response to optimal TKI treatment based on the ELN CML 2013 recommendations from the clinical point of view as a physician. Careful cytogenetic and molecular monitoring could help to select the most convenient TKI drug and to optimize TKI treatment. Excessive monitoring may have an economic cost, but failure to optimize TKI treatment may result in CML disease acceleration and death.

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Section: Practical Problems In the Long-term Monitoring Of Tki Treatmmentioning

confidence: 99%

Monitoring the Response to Tyrosine Kinase Inhibitor (Tki) Treatment in Chronic Myeloid Leukemia (Cml)

Haznedaroğlu

2013

Mediterr J Hematol Infect Dis

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“…On the other hand, in the current study the treatment with olmesartan reduced mostly all hematological parameters but these changes not significantly from normal animals. In agreement, the stimulation of the angiotensin type 1 receptor by angiotensin II stimulate activities of the erythropoietin, thrombopoietin and other hematopoietic cytokines during normal hematopoiesis and in myeloproliferative neoplasms [21] so blocking of angiotensin type 1 receptor by olmesartan reduced hematological parameters. In the same time olmesartan (30 mg/kg) produced no significant changed in AST and ALT enzymes when compared to normal animals.…”

Section: Discussionmentioning

confidence: 69%

Assessment of the Safety of Olmesartan in Combination with Sorafenib in Mice Bearing Ehrlich’s Ascites Carcinoma

Abd‐Αlhaseeb¹,

Zaitone²,

Abou-El-Ela³

et al. 2013

JCT

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Sorafenib was the first multikinase inhibitor to be approved for use in metastatic renal cell carcinoma. Olmesartan medoxomil used in treatment of hypertension and was reported to inhibit angiogenesis in several models. The present study was designed to assess the safety of a combination of sorafenib plus olmesartan compared to monotherapies in mice bearing Ehrlich's ascites carcinoma cell line. Mice were divided to seven groups, 1) normal mice, 2) Ehrlich's ascites carcinoma control, 3-5) olmesartan (3, 10, 30 mg/kg/day), respectively, 6) sorafenib (30 mg/kg/day) and 7) the combination group: mice received olmesartan (30 mg/kg/day) plus sorafenib. All drug treatments continued for 21 days. At the end of the experiment, a complete blood count was performed and kidney and liver functions were estimated. The combination therapy produced a non-significant change in most of the measurements of complete blood count and liver enzymes when compared to normal animals. On the other hand, the combined therapy significantly increased blood urea nitrogen when compared to normal group but did not change the serum creatinine level. Concomitant administration of olmesartan with sorafenib did not significantly augment the toxicity of the later. Therefore; olmesartan might be a safe candidate with sorafenib in treatment of cancer if clinical data proved the benefit of this combination.

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“…Previously designed primer-probes were used [28]. mRNA levels were normalized to CYPA and B-ACTIN genes.…”

Section: Methodsmentioning

confidence: 99%

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

Tatonyan

Sayitoğlu

et al. 2014

Tjh

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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.

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Local hematopoietic renin-angiotensin system in myeloid versus lymphoid hematological neoplastic disorders

Cited by 13 publications

References 41 publications

Monitoring the Response to Tyrosine Kinase Inhibitor (Tki) Treatment in Chronic Myeloid Leukemia (Cml)

Monitoring the Response to Tyrosine Kinase Inhibitor (Tki) Treatment in Chronic Myeloid Leukemia (Cml)

Assessment of the Safety of Olmesartan in Combination with Sorafenib in Mice Bearing Ehrlich’s Ascites Carcinoma

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

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