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

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.