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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We refer to the diagnostic possibilities in T-phenotype acute lymphoblastic leukemia. Immunophenotyping based on the proof of T-differentiation antigens by means of specific monoclonal antibodies and assessment of the E receptor, as well as examination of enzymatic activities of adenosine deaminase and purinenucleoside phosphorylase, were performed. Thirty patients with acute lymphoblastic leukemia of T-phenotype were examined. The monoclonal antibodies used demonstrated a heterogeneity in this type of leukemia reflecting the stage of thymocyte differentiation. The cells of some patients with T-phenotype acute lymphoblastic leukemia expressed simultaneously the common acute lymphoblastic leukemia antigen and Ia molecules. Examination of enzyme activities demonstrated a characteristic pattern with a significantly increased adenosine deaminase activity and simultaneously decreased purinenucleoside phosphorylase activity in T-phenotype acute lymphoblastic leukemia. The unfavorable course of disease in patients with T-phenotype acute lymphoblastic leukemia was demonstrated analyzing a group of 50 children with acute lymphoblastic leukemia. By means of statistical methods the cumulative rate of children surviving with acute lymphoblastic leukemia of common and T-phenotypes have been expressed. The results showed the need for a more effective treatment aimed at the T-phenotype of acute lymphoblastic leukemia.
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PMID:Diagnosis and analysis of the clinical course of T-phenotype acute lymphoblastic leukemia. 297 65

This report summarises the current knowledge regarding the clinical utility of biochemical enzyme markers for both diagnostic and therapeutic purposes in acute leukaemia. The enzymes studied most extensively in this field are terminal deoxynucleotidyl transferase, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, and acid phosphatase, esterase, hexosaminidase isoenzymes. For each enzyme, the quantitative and qualitative characteristics in various immunologically defined subclasses of acute leukaemia are described. The quantitative evaluation of enzyme activities represents an adjunctive classification technique which should be incorporated into the multivariate analysis, the "multiple marker analysis." By qualitative characterisation pronounced heterogeneity of leukaemia subsets is uncovered. The application of 2'-deoxycoformycin, a specific inhibitor of adenosine deaminase, and the potential usefulness of two other enzymes as targets for treatment with selective agents is discussed. The concept that gene products expressed at certain developmental stages of normal cells can similarly be detected in leukaemic cells (which therefore seem to be "frozen" or "arrested" at this particular maturation/differentiation stage) is supported by the results obtained in enzyme studies. Besides their practical clinical importance for classification and treatment of acute leukaemias, biochemical enzyme markers constitute a valuable research tool to disclose biological properties of leukaemic cells.
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PMID:Biochemical enzyme analysis in acute leukaemia. 298 4

The multidisciplinary approach of leukemia phenotyping, called multiple marker analysis, led to changes in the classification systems of normal hematopoiesis and leukemic cells, and introduced the use of a biological and functional definition of leukemia, rather than merely morphological-cytochemical descriptions. Two major conclusions can be drawn from the findings of multiple marker analysis: 1) differentiation of leukemia is not abnormal but blocked ("maturation arrest"), and leukemic cells retain normal maturation-linked markers; and 2) no leukemia specific marker could be detected so far. Although leukemic cells show general qualitative features in common with normal cells, some quantitative characteristics of these similar attributes are peculiar to leukemic blasts. Qualitative and quantitative enzymological characteristics help to identify the cell lineage involved and to determine the developmental point at which maturation arrest occurs. The expression of isoenzymes is often linked to the presumptive sequence of developmental stages. Subsets within ALL subtypes showed pronounced modifications in their isoenzyme patterns associated with increasing maturity. Thus, enzyme markers can provide refined definitions of subgroups by biochemical criteria. Based on recent observations using the enzyme markers TdT, adenosine deaminase, 5'-nucleotidase, purine nucleoside phosphorylase, acid phosphatase, and hexosaminidase, a scheme of enzymological expression in the various commonly accepted subtypes of acute lymphoid leukemia and acute nonlymphoid leukemia is presented. Enzyme marker analysis represents a useful tool as an adjunctive method in multiple marker analysis for assessing diagnosis, prognosis, and the evolutionary and pathogenetic mechanisms underlying the spectrum of leukemia subtypes. Furthermore, enzyme marker analysis may provide further insight into certain aspects of the pathobiology of leukemia which might not be elucidated by other methods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Significance of enzyme markers as a part of multiple marker analysis in leukemia research. 300 Feb 10

Investigations of the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP), and ecto-5'-nucleotidase (5'NT) have been shown to be of value in defining subsets of lymphoid malignancies. We have studied the activities of these enzymes in the circulating malignant cells of 35 patients with chronic B lymphocytic leukaemia and have correlated the biochemical data with immunological phenotypes. Classification of the cases into those without evidence of secretory activity ('true' CLL, 14 patients) and those with cytoplasmic immunoglobulin (CIg) ('immunocytoma'; 21 patients) revealed that immunocytomas are phenotypically and biochemically associated with more mature features. Malignant cells without CIg were characterized by low activities of ADA, PNP and 5'NT. In malignant cells with evidence of secretory activity (immunocytoma), low activity of ADA was also observed, but the activities of PNP and 5'NT were relatively high and approached the range of normal B lymphocytes. The differences in PNP (P less than 0.05) and in 5'NT (P less than 0.01) between these two groups were significant. Phenotypically the cells without CIg were predominantly associated with IgM (+k light chains) as surface membrane immunoglobulin (SmIg) whereas expression of IgG was more often observed in the leukaemic cells with CIg. No correlation between enzyme patterns and the stage of the disease was apparent. Thus both biochemical and immunological criteria show that cases of CLL vary within a range of maturity and that those with CIg might be more mature in the B cell axis. The present study emphasizes the value of purine enzyme studies in defining subsets of B cell neoplasia.
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PMID:Purine degradative enzymes and immunological phenotypes in chronic B-lymphocytic leukaemia: indications that leukaemic immunocytoma is a separate entity. 300 40

The number of gene assignments to human chromosome 20 has increased slowly until recently. Only seven genes and one fragile site were confirmed assignments to chromosome 20 at the Ninth Human Gene Mapping Workshop in September 1987 (HGM9). One fragile site, 13 additional genes, and 10 DNA sequences that identify restriction fragment length polymorphisms (RFLPs), however, were provisionally added to the map at HGM9. Five mutated genes on chromosome 20 have a relation to disease: a mutation in the adenosine deaminase gene results in a deficiency of the enzyme and severe combined immune deficiency; mutations in the gene for the growth hormone releasing factor result in some forms of dwarfism; mutations in the closely linked genes for the hormones arginine vasopressin and oxytocin and their neurophysins are probably responsible for some diabetes insipidus; and mutations in the gene that regulates both alpha-neuraminidase and beta-galactosidase activities determine galactosialidosis. The gene for the prion protein is on chromosome 20; it is related to the infectious agent of kuru, Creutzfeld-Jacob disease, and Gertsmann-Straussler syndrome, although the nature of the relationship is not completely understood. Two genes that code for tyrosine kinases are on the chromosome, SRC1 the proto-oncogene and a gene (HCK) coding for haemopoietic kinase (an src-like kinase), but no direct relation to cancer has been shown for either of these kinases. The significance of non-random loss of chromosome 20 in the malignant diseases non-lymphocytic leukaemia and polycythaemia vera is not understood. Twenty-four additional loci are assigned to the chromosome: five genes that code for binding proteins, one for a light chain of ferritin, genes for three enzymes (inosine triphosphatase, s-adenosylhomocysteine hydrolase, and sterol delta 24-reductase), one for each of a secretory protein and an opiate neuropeptide, a cell surface antigen, two fragile sites, and 10 DNA sequences (one satellite and nine unique) that detect RFLPs.
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PMID:The map of chromosome 20. 307 44

Total adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities were measured in cell samples from 13 cases of de novo acute leukemia and from three cases of chronic myeloid leukemia in blast crisis (CMLBC). These cases could be separated into lymphoid and nonlymphoid types on the basis of enzyme activity, with two misclassifications. However, PNP activity added little or no discriminatory information. Analysis for expression of the various molecular weight (mol wt) ADA isozymes, ADA1 (40 Kd) and ADA2 (110 Kd), revealed that ADA2 was expressed exclusively in nonlymphoid cells whereas ADA1 was found in both lymphoid and nonlymphoid cell types. Identification of ADA2 divided these leukemia cases into lymphoid and nonlymphoid types with no misclassifications (P = .0002; Fisher's exact test). Acute nonlymphoblastic leukemia (ANLL) with a monocytic component tended to have a greater percentage of ADA2 than ANLL without a monocytic component. These studies suggest that ADA2 may be a novel biochemical marker for an immature nonlymphoid cell.
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PMID:Differential expression of adenosine deaminase isozymes in acute leukemia. 314 Sep 11

After four days of treatment with 10(-8) M TPA, differentiation of the human T-lymphoblastoid cell line MOLT-4 was induced along the T cell lineage, confirmed by a fall in adenosine deaminase and 5'-ectonucleotidase and a rise in purine nucleoside phosphorylase activity. TPA-treated cells became resistant to the cytotoxic effects of 1-beta-D-arabinofuranosylcytosine (Ara-C), 9-beta-D-arabinofuranosyladenine (Ara-A), and 2-chlorodeoxyadenosine. This was, in part, due to the altered cell cycle distribution (accumulation of cells in the G1 phase), since the toxicity of Ara-C and Ara-A is S phase specific. The diminished rate of Ara-C transport concomitant with Ara-CTP formation after TPA treatment is considered to be the biochemical basis for this acquired resistance.
Leukemia 1988 Jul
PMID:Changes in sensitivity to anticancer drugs during TPA-induced cellular differentiation in a human T-lymphoblastoid cell line (MOLT-4). 326 Jun 48

A new antimetabolite, 2'-deoxycoformycin (pentostatin), has striking antitumor activity in several lymphoid neoplasms. Isolated from cultured soil organisms, this purine analogue is a potent inhibitor of adenosine deaminase (ADA), and is thus selectively toxic to lymphocytes. Early clinical trials showed that high doses of pentostatin caused severe and unpredictable toxicity, but responses in refractory lymphoid malignancies were encouraging. Careful pharmacologic studies led to the definition of a safe and effective low weekly dose, at which protracted ADA inhibition occurs in neoplastic cells. The most sensitive tumor identified is hairy cell leukemia, in which durable remissions are achieved in more than 90% of patients with a relatively brief course of treatment. Other responsive diseases include chronic lymphocytic leukemia, prolymphocytic leukemia, mycosis fungoides, and acute T-cell lymphoma or leukemia. Response has been seen in acute lymphocytic leukemia, but the higher doses required are substantially more toxic. Pentostatin is valuable for treatment of indolent lymphoid malignancies and may be useful in non-cancer-related lymphocyte research.
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PMID:2'-Deoxycoformycin (pentostatin) for lymphoid malignancies. Rational development of an active new drug. 328 67

Laboratory and clinical data relating to the use of 2'-deoxycoformycin in human disease are reviewed. Pentostatin is an inhibitor of adenosine deaminase, an enzyme that is important for purine metabolism, but more than one mechanism may be involved in its cytotoxic action. Early studies with dCF employed large doses and for the most part were conducted in patients with acute lymphocytic leukaemia: responses were brief and relatively few, and severe renal, hepatic, and central nervous system toxicity were encountered, leading to temporary abandonment of clinical trials. More recently, it has been shown that dCF is effective in much smaller doses, with considerably less toxicity. It has proved to be more effective in low-grade lymphoid malignancies (chronic leukaemias, indolent lymphomas) than in more undifferentiated neoplasms (acute leukaemias, lymphoblastic and immunoblastic lymphomas), and is outstandingly effective in hairy cell leukaemia, both as initial therapy and after failure of splenectomy and interferon. Pentostatin is profoundly immunosuppressive: generally this is considered a disadvantage but its potential therapeutic exploitation merits investigation. Despite extensive knowledge of its biochemical effects, the optimal dose regimen of dCF and the value of combining it with purine antagonists remain to be defined.
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PMID:The role of pentostatin (2'-deoxycoformycin, dCF) in the management of lymphoproliferative malignancies. 333 90

Red-cell adenosine deaminase (ADA) activity in children with Diamond-Blackfan anaemia is significantly increased (1.91 +/- 0.90 U/g Hb) compared to that seen in transient erythroblastopenia of childhood (0.80 +/- 0.16 U/g Hb) or normal individuals (0.61 +/- 0.13 U/g). These data thus further support that measurement of this purine metabolic enzyme is useful in diagnosing the cause of pure RBC aplasia in children. Of interest, however, elevated RBC-ADA activity also is seen in some children with acute leukaemia and other haematologic disorders. In children with acute lymphoblastic leukaemia (ALL), the increase in RBC-ADA activity is proportional to the degree of anaemia. However, the elevated RBC-ADA activity in this leukaemic population is not related to the fetal haemoglobin concentration. These data suggest increased RBC-ADA activity may be a non-specific manifestation of abnormal erythroid stem cell function, an alteration distinct from that seen with reactivation of fetal erythropoiesis. However, since almost all patients with Diamond-Blackfan anaemia manifest elevated RBC-ADA activity, this chemical alteration yet may reflect the specific erythroid differentiation lesion in this disorder.
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PMID:Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases. 334 76


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