Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The new fluorinated adenine analog, fludarabine, has been tested for efficacy in many tumor types over the past ten years. Two other similar nucleoside analogs are currently available for commercial use. Cytarabine is used principally as an antileukemic agent, and vidarabine as an antiviral. Unlike vidarabine, fludarabine is resistant to deactivation by adenosine deaminase. Data from Phase I and II trials suggest that fludarabine is potentially effective in a number of leukemias, including acute lymphocytic leukemia, acute nonlymphocytic leukemia, and chronic lymphocytic leukemia (CLL). Unfortunately, the doses required to achieve adequate response in the acute leukemias (greater than 75 mg/m2) were above the maximum tolerated dose, resulting in intolerable granulocytopenia, thrombocytopenia, and a life-threatening neurotoxic syndrome. In CLL: however, the dose required to achieve a satisfactory response is well within tolerated limits. Long-term survival statistics are not yet available, but historical perspective strongly correlates response to other agents with increased survival times. Toxicities seen at dose regimens of 15-40 mg/m2/d for five consecutive days include somnolence, metabolic acidosis, confusion, fatigue, nausea, vomiting, increase in serum creatinine and aminotransferase concentrations, and pulmonary and hepatic abnormalities. Mild to severe hematologic toxicity has been observed at all dose levels.
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PMID:Fludarabine: a review. 206 37

We studied the activity of serum adenosine deaminase (ADA) and its isozyme in 36 leukemic patients (16 ANLL, 11 ALL, and 9 CML) and 8 MDS. Isozyme was measured by erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibitory assay. This assay was simple and reliable. The appearance rate of abnormally high ADA value were 81.24% for ANLL, 100% for ALL, 77.8% for CML and 37.5% for MDS. The ADA level became high when MDS turned into overt leukemia. In isozyme pattern, there was a clear difference between ANLL and ALL. The isozyme I/II ratio was significantly higher (p less than 0.001) in ALL than ANLL. Lymphoblastic crisis of CML also had a high isozyme I/II ratio. There was a correlation between isozyme I and absolute number of peripheral blasts in ALL (r = 0.768). When observed time sequentially, ADA and isozyme changed correlatively with the number of blasts counts. Serum ADA and its isozyme are useful parameters both for leukemic diagnosis and treatment.
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PMID:[Serum adenosine deaminase and its isozyme activity in leukemia and MDS]. 223 54

We measured the levels of adenosine deaminase (ADA) and immunosuppressive acid protein (IAP) in 10 patients with acute myeloid leukemia (AML), 5 with acute lymphoblastic leukemia (ALL), 8 with chronic myeloid leukemia (CML), 7 with myelodysplastic syndrome (MDS), 5 with malignant lymphoma (ML), 3 with multiple myeloma (MM) and one with adult T cell leukemia. On admission, the level of IAP was abnormally high in all cases of AML and ALL 50% of CML cases, 71.4% of MDS cases, 60% of ML cases and none of MM cases. ADA was elevated in all cases of ALL, 77.8% of AML and CML cases, 57.1% of MDS cases, 60% of ML cases and 33.3% of MM cases. In 7 patients with AML, the level of IAP returned to normal when they achieved complete remission. On the other hand, the level of ADA had already returned to normal even during induction therapy. ADA showed a positive correlation with the absolute number of peripheral blasts and lactic dehydrogenase both in AML and ALL. These results suggest that ADA indicates the activity of leukemia and IAP indicates the immunocompetence of the host.
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PMID:[Combination assay of IAP and ADA in hematologic malignancies]. 238 Oct 93

The activities of the enzymes cytidine deaminase (CDD), deoxycytidine kinase (dCK), adenosine deaminase (ADA), and purine nucleoside phosphorylase (PNP), have been investigated in the promyelocytic leukemia cell line HL60. The activities of the enzymes corresponded well with that seen in acute myeloid leukemia cells except, that the CDD activity was very low in the HL60 cells. Induction of differentiation in HL60 cells by 1,25 dihydroxy D3 resulted in an increase in CDD from 12 to 247 nmol/h/mg and a decrease in ADA from 1326 to 896 nmol/h/mg, while the activities of dCK, and PNP were unchanged. Retinoic acid, another used inducer of differentiation, gave no changes of the enzyme activities. The increase in CDD activity induced by 1,25 dihydroxy D3 was prevented by inhibition of protein synthesis, whereas inhibition of proliferation of the cells did not abolish the increase of CDD. The changes correspond well with the differences seen between immature and mature myeloid cells. The results may have consequences for the interpretation of results obtained with cytostatics, which are metabolized by the enzymes.
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PMID:Changes in the activities of cytidine deaminase during differentiation of HL60 cells induced by 1,25 dihydroxy D3. 316 86

2-Bromo-2'-deoxyadenosine (BdA) is one of a group of recently synthesised halogenated deoxyadenosine analogues that are relatively resistant to inactivation by adenosine deaminase (ADA). Its activity has been studied in human acute myeloid leukemia (AML) in vitro. In these studies BdA behaved as a cycle-active, phase-active agent that blocked cells at the G1-S transition. It did not exhibit significant cross-resistance with cytosine arabinoside (Ara-C) in either clinical AML samples (from patients who exhibited Ara-C resistance in vivo) or in HL60 in which Ara-C resistance had been induced in vitro. Deoxycytidine kinase levels were not reduced in resistant lines. Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an adenosine deaminase (ADA) inhibitor, with BdA produced a simple additive response without the dramatic synergism reported when it is used with deoxyadenosine. This is consistent with the idea that BdA is a poor substrate for ADA. This group of compounds warrants further investigation to determine their suitability for clinical use, especially in situations where Ara-C resistance is likely to be a problem.
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PMID:Lack of cross-resistance between cytosine arabinoside and a new halogenated nucleoside analogue, 2-bromo-2'-deoxyadenosine in human acute myeloid leukaemia cells. 349 52

Three enzymes concerned in purine degradation, 5'nucleotidase (5'NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) have been measured biochemically in the bone marrow or peripheral blood blasts from 75 patients with acute leukaemia, from 18 patients with blast crisis of chronic granulocytic leukaemia and in the bone marrow and peripheral blood lymphocytes from 14 normal donors. Characteristic patterns among the different sub-types of acute leukaemia have been detected, with high ADA, low 5'NT and PNP in Thy-ALL, high 5'NT and ADA in c-ALL, high PNP and low ADA in AML. The cells in CGL blast transformation resembled the enzymatic pattern of either AML or c-ALL respectively. However, no significant correlation was found between any pair of enzymes in any group of leukaemia, normal bone marrow or peripheral blood lymphocytes studied here.
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PMID:5'nucleotidase, adenosine deaminase and purine nucleoside phosphorylase activities in acute leukaemia. 629 84

Lymphocytes from patients with chronic lymphatic leukemia, acute lymphoblastic leukemia and acute myeloid leukemia have been characterized by the activity of two enzymes involved in purine metabolism--adenosine deaminase and purine nucleoside phosphorylase and by the analysis of surface marker expression. The data obtained suggest that the activity of enzymes of purine metabolism can be used as a complementary diagnostic marker to conventional cell surface characteristics for the classification of lymphoproliferative diseases, especially in the case of T-acute lymphoblastic leukemia. The changes of the purine pathway enzymes may prove to be useful also as therapeutic determinants in hemopoietic neoplasia, particularly in the lymphoid malignancies.
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PMID:Enzymes of purine metabolism and membrane phenotype in malignant cells of some leukemia patients. 644 Nov 24

The combination of 2'-deoxycoformycin (DCF), a potent adenosine deaminase (ADA) inhibitor, and 9-beta-D-arabinofuranosyladenine (Ara-A) was used in a patient with acute nonlymphocytic leukemia refractory to all conventional modes of therapy. DCF was given by periodic iv injections to ablate ADA activity. Ara-A was given by continuous iv infusion at an initial dose of 1.5 mg/kg/day, with progressive increases to 6 mg/kg/day. With adequate ADA suppression (less than 2 x 10(-2) mumols of inosine/hr/10(6)h cells), the Ara-A decreased the absolute peripheral blood myeloblast count from 36,332 to 780/microliter. The patient experienced no renal, hepatic, or neurologic complications during therapy.
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PMID:2'-deoxycoformycin (DCF) and 9-beta-D-arabinofuranosyladenine (Ara-A) in the treatment of refractory acute myelocytic leukemia. 697 33

The current status of three drugs of clinical interest to the National Cancer Institute is reviewed. m-AMSA, a drug with a wide spectrum of activity in murine tumors, is now in phase II trial and has shown itself to have a high order of activity in acute nonlymphocytic leukemia. Dihydroxyanthracenedione, a compound with some of the characteristics of anthracyclines but with no cardiac toxicity in animal toxicology studies, is in phase I evaluation. Deoxycoformycin, an adenosine analog which is a potent inhibitor of adenosine deaminase, has shown moderate activity in acute leukemia patients in phase I trials, and has the potential to produce synergistic antitumor toxicity when used with arabinofuranosyladenine.
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PMID:Current status of clinical trials of m-AMSA, dihydroxyanthracenedione, and deoxycoformycin. 697 70


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