Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood or bone marrow of 24 patients with chronic myeloid leukemia (CML) were characterized for their surface membrane marker profiles using flow cytometry and fluorescence microscopy. Purine metabolism enzyme activities were compared with membrane immunophenotype and cytochemical stains. CML subtypes were correlated with the expression of surface membrane antigens detected by the monoclonal antibodies. On the basis of immunophenotyping we found the following characteristic marker profiles: In stable phase of CML (CML-SP)-CD15, CD11b, CDw65, CD13, in accelerated phase of CML (CML-AP)-CD15, CDw65, CD11b, CD13 and CD33, in myeloid blastic phase of CML(CML-BP-M)-CD13, CD33, HLA-DR, CD11b, CD15, CDw65, in myeloid and lymphoid (mixed) blastic phase of CML (CML-BP-M+L)-CD13, CD33, CD34, HLA-DR, CD11b, CD10 and in chronic myelomonocytic leukemia (CMML)-CD14, CDw65, CD11b, CD33 and HLA-DR. Analysis of purine metabolism enzyme activities showed that there was a correlation between the values of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) and various types of CML. ADA levels in CML-SP, CML-AP and CMML were comparable with those in normal cells. In CML-BP-M, which represents proliferation of less mature myeloid cells (similar to less mature AML subtypes), ADA activity increased and PNP activity decreased. ADA activity was significantly different between control group and CML-BP-M (p < 0.01), between CML-SP and CML-BP-M (p < 0.05). The values of PNP activity were the highest in stable phase of CML (125 pkat. 10(-6) cells) and the lowest (23 pkat.10(-6) cells) in CML-BP-M+L. PNP activity in the other groups corresponded to control values. High ADA/PNP ratio was found in CML-BP-M and CML-BP-M+L (0.7 and 2.0, respectively) in comparison to CML-SP (0.2). It follows from our results that ADA/PNP ratio enables to discriminate between stable and blast phases of CML (p < 0.01). The level of the cytochemical enzymes (CHAE, MPO, SBB, ANAE and 5' NT) varied and reflected the degree of cell differentiation and maturation. CHAE and MPO were characteristic enzymes for CML, ANBE for CMML and 5' NT for CML-BP-lymphoid.
 ...
PMID:Chronic myeloid leukemia: correlation between purine metabolism enzyme activities and membrane immunophenotype. 761 76

A total of 34 AML patients with heterogenous age distribution (from 2 years up to 82 years) were observed. Purine metabolism enzyme activities were compared and correlated with membrane immunophenotype. Analysis of bone marrow and peripheral blood samples based on FAB criteria and immunologic phenotyping of acute myeloid leukemia (AML) provided useful--either confirmatory or contradictory-information on the distribution of M1-M6 patients demonstrating a predominance of M1+M2 and M4 groups (44% and 32.4%, respectively). In contrast, it was demonstrated that less frequent subtypes were M3 and M6 (5.9% and 2.9%, respectively). AML subtypes were correlated with expression of surface antigens detected by the following monoclonal antibodies: CD13, CD33, CDw65, CD11b, CD15, CD14, HLA-DR and CD34. On the basis of immunophenotyping we found the following characteristic markers: M1, M2-CD34, HLA-DR, CD13, CD33, CDw65; M3-CD13, CD33, HLA-DR (negative); M4, M5-CDw65, CD14, CD13, CD33 and HLA-DR. CD14 was confirmed to be a typical marker for discriminating myeloid from monocytoid FAB AML subtypes. Analysis of purine metabolism enzyme activities showed that there is a correlation between the values of adenosine deaminase and purine nucleoside phosphorylase and various immunotypes of AML. High ADA/PNP ratio (> 1.0) was found in M1, M2, M3 subtypes. It was due to the increased level of ADA activity (> 100 pkat.10(-6) cells), though these activities overlapped to a certain extent. It was shown that PNP activity simultaneously decreased. With maturation of cells within AML lineage ADA activity decreased and PNP activity increased. This corresponded with ADA/PNP ratio that was < 1.0 in cells of more mature AML subtypes. We found that the enzymatic values were characteristic mainly in cells of M5 (monocytic) AML subtype and were characterized by decreased values of ADA activity with a simultaneous increase in PNP activity. It follows from our results that ADA/PNP ratio enables to discriminate between myeloid and monocytoid subtypes of AML.
 ...
PMID:Acute myeloid leukemia: correlation between purine metabolism enzyme activities and membrane immunophenotype. 828 64

Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.
...
PMID:The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27. 2762 30