Overexpression of the local bone marrow renin-angiotensin system in acute myeloid leukemia

• Published in: Journal of the National Medical Association 2007, Vol.99 (1), p.57-63
• Main Authors: BEYAZIT, Yavuz, AKSU, Salih, GOKER, Hakan, OZCEBE, Osman I, HAZNEDAROGLU, Ibrahim C, KEKILLI, Murat, MISIRLIOGLU, Muge, TUNCER, Serdar, KARAKAYA, Jale, KOCA, Ebru, BUYUKASIK, Yahya, SAYINALP, Nilgun
• Format: Article
• Language: English
• Subjects: Acute Disease; Angiotensins - genetics; Biological and medical sciences; Bone Marrow - chemistry; Gene Expression Regulation, Leukemic; General aspects; Hematologic and hematopoietic diseases; Leukemia, Myeloid - physiopathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Oligopeptides - analysis; Peptidyl-Dipeptidase A - genetics; Renin - genetics; Renin-Angiotensin System - physiology
• ISSN: 0027-9684; 1943-4693

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. Angiotensin-converting enzyme (ACE) hyperfunction may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow microenvironment, finally removing the antiproliferative effect of AcSDKP on the hematopoietic cells and blasts. The aim of this study is therefore to search those major RAS components simultaneously in the leukemic blast cells taken from the bone marrow of patients with acute myeloid leukemia (AML). Bone marrow aspiration materials were obtained from 10 patients with AML (8 males, 2 females; median age 48.5 years) and 8 patients with nonmalignant hematological disorders (6 males, 2 females; median age 45 years). EDTA-treated bone marrow samples were stored at -70 degrees C until analysis. Total RNA was extracted from 200-microl bone marrow samples by High Pure RNA Isolation Kit. The medians of expression ratios of AML patient samples have been found 0.736 (IQR 1.359), 0.540 (IQR 0.725), and 0.075 (IQR 0.002) for ACE, ANG and REN genes, respectively. All three gene expressions were found to be significantly higher in the bone marrow samples of AML patients. In this study, the expression of the mRNAs of the major RAS components-namely ACE, renin and angiotensinogen-in human bone marrow samples were quantified by reverse transcription-polymerase chain reaction (RT-PCR) to confirm the presence of the local bone marrow RAS. Elucidation of the pathological activity of the local RAS-mediated regulation of the leukemogenesis is both pathobiologically and clinically important, since the angiotensin peptides represent a molecular target in the disease management.