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.

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by recurrent inflammation and ulcerations of colonic mucosa and an inappropriate and delayed healing. Adenosine deaminase (ADA) is a cytoplasmic enzyme involved in the catabolism of purine bases, capable of catalyzing the deamination of adenosine, forming inosine in the result process. Although ADA has been shown to increase in several inflammatory conditions, there are no literature data indicating an alteration in UC. This study evaluated the activity of total ADA in serum of 43 patients with UC and 18 healthy controls. Patients' age, disease duration, drug intake, and other medical history were all noted for each subject. Complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined for both patients and controls. Correlation analysis was also performed between ADA and other inflammation markers of UC. Serum mean ADA levels were 11.12 ± 2.03 and 7.99 ± 2.04 U/l for patients with UC in active state and in remission and 8.55 ± 2.26 U/l in the healthy control group. Mean serum ADA levels were significantly elevated in active UC patients compared with patients with UC in remission and control groups. Overall accuracy of ADA in determination of active UC was 83.7 with sensitivity 83.3%, specificity 84.2%. Serum ADA levels were found to be elevated in UC patients in active state suggesting a partial role of activated T-cell response in the disease pathophysiology. Further randomized controlled studies are warranted to demonstrate the role of ADA in UC patients, with a special interest in specifically targeted therapies against ADA for achieving disease remission.

Hepatocellular carcinoma (HCC) has poor long-term prognosis so we need new diagnostic techniques and markers to detect HCC in the early phases. The aim of this study was to analyze the levels of serum mean platelet volume in HCC. The clinical data of 230 subjects with normal, chronic hepatitis, cirrhosis and HCC were retrospectively analyzed at our hospital between January 2009 and December 2009. The levels of MPV were determined in patients with liver disease and compared between patient groups and with healthy persons. Serum MPV levels were significantly increased compared to the patients with chronic hepatitis, cirrhosis, and the control group (p<0.01). The cut-off value for MPV for the detection of HCC in cirrhotic patients was calculated as ≥9.2fl using ROC analysis [Sensitivity: 68.3%, specificity: 62.1%, AUC: 0.676 (0.580-0.773), p<0.001]. Additionally, serum MPV levels show higher sensitivity for diagnosis of HCC than AFP. An AFP of more than 7.4IU/mL and an MPV of ≥9.2fl, both put together, had a specificity of 95.2%, while when used separately, they have a sensitivity of 87.5%. MPV may be a potential or adjunctive marker of HCC in patients with chronic liver disease.

Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting hematopoiesis. Angiotensin II type 1a (AT1a) receptors are present on the CD34+ hematopoietic stem cells. Angiotensin II stimulates the proliferation of bone marrow and umbilical cord blood hematopoietic progenitors. There are preliminary data that local RAS might also be involved in leukemogenesis. ACE hyper-function may lead to the acceleration of negative hematopoietic regulator peptide, AcSDKP, metabolism, which in turn lowers its level in the bone marrow micro-environment, finally removing the anti-proliferative effect of AcSDKP on the hematopoietic cells and blasts. Renin expression could have a role on the leukemia development and angiotensin may act as an autocrine growth factor for acute myeloid leukemia (AML) cells. The aim of this study is to search ACE (CD 143) surface antigen by flow-cytometric analyses on the leukemic blast cells taken from the bone marrow of the patients with AML. Bone marrow aspiration materials and peripheral blood samples were obtained from 11 patients with AML (eight males, three females; aged 46 (range 26–67) years) and six patients with non-malignant hematological disorders (four males, two females; aged 56 (range 22–71) years). ACE (CD 143) surface antigen was shown to be over-expressed in leukemic myeloid blast cells. ACE is positively correlated with bone marrow blast count. 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.