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)

The purpose of this report is to compare measurements of enzymatic activities and cell surface markers as methods of distinguishing subtypes of lymphoid leukemias of childhood. Twenty-six children ages 2-15 yr were studied. Terminal deoxynucleotidyl transferase (TdT) activity was high in blasts from all 20 children with either null or T cell acute lymphoblastic leukemia. The activity of adenosine deaminase per cell was higher (P less than 0.005) and that of TdT lower (p less than 0.05) in T than in null cell lymphoblasts, although there was some overlap in values. Blasts from 3 children with acute lymphoid leukemia were positive for surface-associated immunoglobulins. The neoplastic lymphoid cells from these children differed from T and null cell leukemic lymphoblasts by having very low levels of TdT and adenosine deaminase activity. Measurements of adenosine deaminase and TdT may complement measurements of cell surface markers and distinguish biochemical subtypes of acute lymphoid leukemia.
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PMID:Adenosine deaminase, terminal deoxynucleotidyl transferase (TdT), and cell surface markers in childhood acute leukemia. 28 Dec 53

An adult patient with acute lymphoblastic leukemia associated with a 14q+ marker chromosome is presented. The abnormality resulted from a translocation of material from the long arm of chromosome 11. The leukemic cells were found to be B cells on the basis of surface immunoglobulins, lack of receptors for sheep erythrocytes, and a characteristically low level of adenosine deaminase activity. In other patients with ALL studied by us or reported by others in whom chromosome banding was done, a 14q+ chromosome was present in only one instance, also a case of B cell ALL. These two cases are the only examples of B cell ALL studied with chromosome banding reported to date. The frequent occurrence of a 14q+ chromosome in other malignant lymphoproliferative diseases of B cell origin suggests that a general association may exist between the 14q+ abnormality and B cell neoplasms. Cytogenetic analysis may therefore be useful in defining subtypes of ALL and in relating specific chromosomal abnormalities to lymphoproliferative disorders.
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PMID:B cell acute lymphoblastic leukemia (ALL) with a 14q+ chromosome abnormality. 31 Jun 97

A competitive radioimmunoassay for a saline-soluble human thymus-leukemia-associated antigen (HThy-L) was applied for quantitation of this antigen in leukemia and normal hematopoietic cell lines. Highly increased quantities of HThy-L were detected in all T-cell leukemia lines tested, regardless of the presence or absence of receptors for sheep erythrocytes. This elevated level of HThy-L in combination with high terminal deoxynucleotidyl transferase and adenosine deaminase activities and the presence of a T-lymphocyte-specific surface antigen appear to represent stable phenotypic characteristics of T-cell lines. Most normal B-cell lines had low quantities of HTy-L. The level of HThy-L was slightly elevated in a considerable number of lymphoma B-cell lines and in all non-T, non-B leukemia cell lines tested. No relationship existed between quantities of HThy-L and an expression of different surface immunoglobulin isotypes in B-cell lines. Low quantities of HThy-L were detected in leukemia myeloid and myeloma cell lines as well as in B-cell leukemia lines originating from patients with B-cells acute lymphoblastic leukemia. Apparently, the increased quantities of HThy-L in T-cell leukemia lines may be related to certain stages of T-cell differentiation at which leukemia cell transformation occurs.
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PMID:Quantitation of human thymus-leukemia-associated antigen in established hematopoietic cell lines by radioimmunoassay. 31 16

A causal relation between the enzyme, adenosine deaminase (ADA), and immune dysfunction is well known: patients with congenital inactivity of ADA invariably suffer of severe combined immunodeficiency. In contrast, we found in patients treated with immunosuppressive drugs increased ADA enzyme activity. Previous findings on ADA activity in acute leukemias are until now controversial. We found normal to increased ADA activity in children with acute lymphatic leukemia (ALL) and acute myeloid leukemia (AML) in remission as long as they were treated with cytostatic drugs. In the group of cured leukemics (in continuous remission after suspension of the therapeutic regimen) the ADA activities were normal. These findings do not exclude a heterogeneity within the leukemia group. They do not explain the signs of cellular immunodeficiencies well known in patients with acute leukemias.
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PMID:[Adenosine deaminase activity in blood cells; influence of cytostatic therapy in patients with acute leukemia and with renal transplants (author's transl)]. 39 66

A lack of adenosine deaminase activity has been associated with severe combined immunodeficiency and decreased enzyme activity observed in acute lymphocytic leukemia. We have measured enzyme activity in lymphocytes, red blood cells, and plasma of patients with a variety of metastatic tumors. Patients with tumor had a significantly lower erythrocyte adenosine deaminase activity (p less than 0.025) and statistically higher enzyme activity in their lymphocytes (p less than 0.010) when compared with control plasmaphoresis donors. Interestingly, blood type A tumor patients showed a significant decrease in their erythrocyte enzyme concentration compared with blood group A controls (p less than 0.001) as well as a collective group of type B and O tumor patients (p less than 0.001). Type A patient lymphocyte adenosine deaminase activity was not increased and was not statistically different from control group A donors. Tumor patients with blood groups B and O considered collectively had a statistically significant increase in their lymphocyte enzyme concentration compared with group B and O controls (p less than 0.001).
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PMID:Adenosine deaminase levels in blood type A patients with metastatic tumor. 124 85

Three established human T-cell lines, HPB-MLT, HPB-ALL and PEER, were characterized and tested for their sensitivity to deoxyadenosine (dAdo) plus deoxycoformycin (dCoF). Phenotypic characterizations showed that all three cell lines had receptors for peanut agglutinin (PNA) and soybean agglutinin (SBA) while HPB-MLT and HPB-ALL, but not PEER, expressed the cortical thymocyte-specific marker, CD1. The majority of HPB-MLT cells (88%) expressed only CD4 but not CD8 antigen while most HPB-ALL cells (81%) co-expressed CD8 and CD4 antigens. PEER cells were negative for both CD8 and CD4. These three T cell lines showed differential sensitivity to dAdo plus dCoF in consequent tests. dAdo or dAdo plus dCoF (1 microM) had no effect on the growth, or DNA and RNA synthesis of HPB-MLT cells while the combination of dAdo and dCoF partially inhibited cellular growth and DNA and RNA synthesis of HPB-ALL cells. Further, the growth and DNA and RNA synthesis of PEER cells were strongly inhibited by the combination of dAdo and dCoF. This high sensitivity to dAdo plus dCoF reflected an immature phenotype of PEER cells despite its expression of CD3. Flow cytometric analysis of PEER cells demonstrated disappearance of the G2/M phase cells from the cell cycle after treatment with dAdo plus dCoF. Measurements of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities in all three cell lines, however, did not establish correlations between purine metabolizing enzyme activities and the differential sensitivities to dAdo plus dCoF. In sum, we report here three T-cell lines of different phenotypes that displayed significantly different sensitivities to dAdo plus dCoF which may facilitate investigations on the mechanisms of ADA deficiency.
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PMID:Characterization of three T-lymphoid cell lines with distinct sensitivities to deoxyadenosine plus deoxycoformycin. 137 28

Forty-nine children with recurrent acute lymphoblastic leukemia (ALL) were entered into a randomized Phase II trial evaluating 2'-deoxycoformycin (dCF) alone or in combination with adenine arabinoside (ara-A). 2'-Deoxycoformycin is an inhibitor of adenosine deaminase (ADA), an enzyme found in relatively high amounts in malignant lymphoid cells. Ara-A inhibits DNA polymerase and DNA synthesis. Because its efficacy in vivo as an anticancer agent is limited by its rapid inactivation by ADA, ara-A was combined with dCF to produce cytoreductive levels of ara-A. Twenty-four patients were assigned to receive dCF alone and 25 to receive the combination. No patient responded to dCF alone, and one patient developed a complete remission after treatment with the combination. The toxicity of dCF alone was minimal, except for one patient who became obtunded on day 5 following the first cycle of therapy. In contrast, five patients developed severe toxicity with the combination, including renal failure (three patients), hepatic failure (three patients), and neurologic toxicity (two patients). These results indicate that, at the doses and schedule used in this study, the combination of dCF and ara-A has significant toxicity and minimal activity against recurrent ALL in children.
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PMID:Lack of significant activity of 2'-deoxycoformycin alone or in combination with adenine arabinoside in relapsed childhood acute lymphoblastic leukemia. A randomized phase II trial from the Childrens Cancer Study Group. 144 10

Many reports have described the relationship of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities with the immunological subclasses of acute lymphoblastic leukemia (ALL). The clinical significance of these enzymes in leukemias is not yet completely understood. We performed a study in 83 children with untreated ALL to establish the relationships of ADA and PNP to clinical outcome, in vitro drug resistance and differentiation stage of B-cell lineage ALL. ADA and PNP activities were determined radiochemically. In vitro resistance to 6-thioguanine (6-TG) was determined with the MTT assay. ADA activity was not different between proB- and cALL cases but decreased in the sequential differentiation stages cALL----preB-ALL----B-ALL. The PNP level was not different between the four stages of B-lineage ALL. Patients with cALL/preB ALL with low ADA activities had a significantly poorer probability of survival (p = 0.005) than patients with high ADA levels. Patients with cALL/preB ALL with low PNP activities showed a non-significant trend for a poorer prognosis (0.05 less than p less than 0.10) than patients with a high PNP level. Low ADA and PNP activities were not related to in vitro resistance to 6-TG. We conclude that ADA decreases and PNP remains constant in sequential differentiation stages of B-lineage ALL. Patients with precursor B-lineage ALL with low activities of ADA have a poorer prognosis than those with high activities of these enzymes. No relationship could be detected between ADA or PNP activity and resistance to 6-TG.
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PMID:Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis. 159 2

Human adenosine deaminase (ADA; EC 3.5.4.4) consists of three isoenzymes: ADA1, ADA1+CP, and ADA2. We developed an electrophoretic technique to distinguish between these three isoenzymes. The isoenzyme pattern was studied in tissue and cell homogenates, as well as in serum from normal subjects and from patients with increased serum ADA who had either hepatitis, infectious mononucleosis, tuberculosis, pneumonia, rheumatoid arthritis, or acute lymphoblastic leukemia (ALL). The highest ADA activity was found in lymphocytes and monocytes. ADA2 could be detected only in monocytes (18% of total ADA activity). It was also the predominant isoenzyme in the sera of controls and all disease groups, except for ALL--the only condition evaluated that is not of an inflammatory nature. We conclude that serum ADA reflects monocyte/macrophage activity or turnover in most diseases studied. The exception is ALL, where serum ADA most probably originates from lymphocyte precursors.
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PMID:Serum adenosine deaminase: isoenzymes and diagnostic application. 162 98

We have previously shown that stimulation of the Ti/CD3 receptor complex on human T-cells potentiates adenylate cyclase activation by adenosine or forskolin. Anti-CD2 receptor antibodies shared with anti-CD3 antibodies the ability to potentiate dose dependently the adenosine- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) accumulation, whereas stimulation of the CD45 receptor had no effect on cyclase activity. Modulation of the CD3 complex with anti-CD3 antibodies was found to decrease the CD2 receptor effect on adenylate cyclase activity greatly. The possible involvement of CD3-stimulated phospholipase C (PLC) activation on the cAMP potentiation was examined using HPB-ALL cells that express a CD3 complex with a defect coupling to PLC. Stimulation of the CD3 complex on HPB-ALL cells had only slight effects on adenosine-stimulated cAMP formation, whereas the effect on forskolin-stimulated cAMP was virtually unchanged. The CD3 effect was further analyzed in Jurkat cell membranes. In contrast to the results obtained after stimulation of intact cells, it was found that OKT3 stimulation of membranes did not potentiate the forskolin response. Finally, we tested whether inhibition of endogenous adenylate cyclase agonist production affected the CD3 effect. Inhibition of adenosine production or adenosine breakdown with 8-p-sulphophenyl theophylline (8-PST) or adenosine deaminase (ADA), respectively, did not alter the CD3 effects. Indometacin, which inhibits prostaglandin production, also had no effect. Together, these data show that stimulation of the CD2 receptor potentiates adenylate cyclase responses by a mechanism that is dependent on CD3 expression. Furthermore, the CD3 effect on cAMP appears to be mediated by two different mechanisms, one which is, and one which is not dependent on PLC. Finally, this effect is not due to an endogenous production of adenylate cyclase agonists.
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PMID:CD3-dependent increase in cyclic AMP in human T-cells following stimulation of the CD2 receptor. 167 13


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