Circulating and local bone marrow renin-angiotensin system in leukemic hematopoiesis: preliminary evidences

Until last the decade, the renin-angiotensin system (RAS) was considered as a circulating endocrine system. It is now known that there are local RASs in many tissues. It has also recently been hypothesized that there exists a local bone marrow (BM) RAS with paracrine/autocrine pathobiological functions. The aim of this study was to detect BM and peripheral blood levels of the essential RAS components in normal and leukemic hematopoiesis. Concentrations of renin and angiotensin-converting enzyme (ACE) were assayed in BM aspirates and in simultaneously drawn peripheral blood samples of 16 pre-chemotherapy leukemic and 10 post-treatment megaloblastic anemia patients with normal blood counts, as controls. In the leukemia group, the ACE concentration was found to be significantly higher in the BM (38+/-6.2 U/l) than in the peripheral blood (29.5+/-5.3 U/l), (p=0.029). In the leukemia group, although the BM renin concentration was higher than the peripheral blood levels (21.3+/-8.3 vs. 18.6+/-6.2 U/l), this difference was not statistically significant (p=0.196). In the control group, mean BM renin levels were insignificantly lower than in the peripheral blood (8.6+/-3 vs. 12.1+/-4.6 pg/ml) (p=0.059). In the leukemia group, serum ACE levels positively correlated with BM and peripheral blood blast percentages (p<0.05). Serum LDH level (p<0.01), BM blast (p<0.05) and peripheral blast percentages (p<0.01) were inversely correlated with serum potassium in the leukemia group.The results of this study can be considered as the preliminary evidence supporting the hypothesis of the presence of a local BM RAS. Further, molecular biologic and immunohistochemical studies are needed to shed light on this important subject. A better understanding of the interrelationships of RAS and hematopoiesis will bring new insights into the pathobiology and even novel therapies for such neoplastic diseases.