Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphisms in Leukemic Hematopoiesis

Akalın, İbrahim

doi:10.4999/uhod.09164

Cited by 8 publications

(12 citation statements)

References 39 publications

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“…7,8 There is preliminary evidence that local BM RAS could affect neoplastic hematopoiesis. [9][10][11][12][13][14][15][16] Over-expression of the angiotensin-converting enzyme (ACE) (CD 143) surface antigen in leukemic myeloid blast cells have been detected by flow cytometric analyses. Moreover, a positive correlation has been found between the ACE and BM blast count.…”

Section: Introductionmentioning

confidence: 99%

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

Tatonyan

Sayitoğlu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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There is preliminary evidence that the local renin-angiotensin system (RAS) could affect neoplastic hematopoiesis. The aim of this study is to search messenger RNA (mRNA) expressions of the essential RAS elements in myeloid and lymphoid hematological neoplastic disorders. Forty-six patients with newly diagnosed myeloid (AML, biphenotypic leukemia, CML) or lymphoid (CLL, NHL, B-ALL, T-ALL) hematological disorders were included in the study. In the lymphoid group, the median expression values of RENIN, ACE1, ACE2 and ANGIOTENSINOGEN (ANGTS) mRNAs were 1.96%, 0.42%, 0.00% and 0.00%, respectively; in the myeloid group, 0.73%, 1.55%, 0.04% and 0.006%, respectively. In the lymphoid group, RENIN levels were significantly higher (p = 0.001), whereas ACE1 and ACE2 levels were significantly higher in the myeloid group (p values were 0.013 and 0.010, respectively). ANGTS levels were similar in both groups. In patients with non-ALL lymphoid malignancies, RENIN expressions were significantly higher when compared to ALL patients (p = 0.004). All patients with active disease had significantly higher RENIN mRNA expression levels than patients without active disease (2.03% vs 0.30%) (p = 0.034). The result of our present study indicates that the activities of local RAS may differ in distinct disease states such as leukemia and lymphomas.

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Section: Introductionmentioning

confidence: 99%

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

Tatonyan

Sayitoğlu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…We investigated ACE I/D gene polymorphisms in patients with haematological malignancies, including acute and chronic leukaemia, myelodysplastic syndrome and multiple myeloma. Our results showed that 80.4 % of the patients had a ID/II genotype compared with 55.9 % in the control group, with a 3.2-fold increased disease risk in the presence of the insertion allele (ID/II) [122].…”

Section: Acementioning

confidence: 58%

Local bone marrow renin–angiotensin system in primitive, definitive and neoplastic haematopoiesis

Haznedaroğlu

Beyazıt

2012

Clinical Science

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The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

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“…Moreover, a positive correlation has been found between ACE and BM blast count. 17 Hence, local BM RAS has been investigated in acute leukaemias 17,18,44,[46][47][48][49] and chronic myeloproliferative disorders, 32,43,[50][51][52][53] and angiotensin has been suggested to act as an autocrine growth factor for AML cells. We investigated the ACE insertion/ deletion (I/D) gene polymorphisms in patients with haematological malignancies including acute and chronic leukaemia, myelodysplastic syndrome and multiple myeloma.…”

Section: Local Haematopoietic Bone Marrow Renin-angiotensin System In Neoplastic Haematopoiesismentioning

confidence: 99%

“…Our results showed that 80.4% of the patients represented the ID/II genotype, compared with 55.9% in the control group, demonstrating a 3.2-fold increased disease risk for the insertion allele (ID/II). 49 Consequently, increased production of AngII by membranebound ACE could result in leukaemic transformation of BM haematopoietic cells by co-ordinated activation of signal transduction pathways via the AT-1 receptor and/or receptor transactivation. 54 Immunohistochemical studies have shown the possible role of ACE/RAS in BM by evaluating ACE expression in normal BM, several myeloproliferative disorders and myelodysplasia.…”

Section: Local Haematopoietic Bone Marrow Renin-angiotensin System In Neoplastic Haematopoiesismentioning

confidence: 99%

Review: Pathobiological aspects of the local bone marrow renin-angiotensin system: a review

Haznedaroğlu

Beyazıt

2010

J Renin Angiotensin Aldosterone Syst

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The local haematopoietic bone marrow (BM) renin-angiotensin system (RAS) mediates pathobiological alterations of haematopoiesis in an autocrine/paracrine/intracrine fashion. Recent data further indicated the existence of angiotensin-converting enzyme (ACE) in human primitive lympho-haematopoietic cells, embryonic, foetal and adult haematopoietic tissues. Human umbilical cord blood cells also express renin, angiotensinogen, and ACE mRNAs. As ACE and other angiotensin peptides function in human haematopoietic stem cells (HSCs) throughout haematopoietic ontogeny and adulthood, local RAS could also have a function in HSC plasticity, and the development of haematological neoplastic disorders. The presence of ACE on leukaemic blast cells within leukaemic BM, on erythroleukaemic cells, ACE-expressing macrophages in lymph nodes of Hodgkin disease, renin activity in leukaemic blasts, angiotensin II as an autocrine growth factor for AML, increased renin gene activity during NUP98-HOXA9 enhanced blast formation, higher levels of BB9/ACE (+) AML isoforms, and altered JAK-STAT pathway as a link between RAS and leukaemia indicated the wide pathobiological aspects of local BM RAS. The comparable biological actions of local RASs throughout the human body (including myocardium, pancreas, pituitary gland, ovary and kidney) represent the true basis for the search of their prominence in tissue functions. Recent data and perspectives of the local BM RAS in health and disease are reviewed in this paper.

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Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphisms in Leukemic Hematopoiesis

Cited by 8 publications

References 39 publications

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

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

Local bone marrow renin–angiotensin system in primitive, definitive and neoplastic haematopoiesis

Review: Pathobiological aspects of the local bone marrow renin-angiotensin system: a review

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