Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients are presented with a chronic lymphoproliferative disorder characterized clinically by splenomegaly, no or discrete lymphnode enlargement, and a varying degree of cytopenia. In blood and bone-marrow smears lymphoid cells of "hairy" appearance are demonstrable which may contain tartrate-resistant acid phosphatase. The finding of a nodular bone-marrow infiltration without fibrosis as well as that of a nodular infiltration of the spleen originating in the white pulp are incompatible with the diagnosis hairy-cell leukemia and place the disease near to chronic lymphocytic leukemia (CLL) or leukemic immunocytoma respectively. A detailed cytologic and cytochemical examination of the infiltrating cells shows deviations from the typical enzymatic pattern of hairy cells and from known enzymatic constellations in CLL and related lymphoproliferative disorders. Thus, we are dealing with an intermediate form, difficult to classify, the separation of which nevertheless seems to be important for therapeutical reasons.
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PMID:[Chronic lymphoproliferative disorder resembling hairy-cell leukemia (author's transl)]. 724 28

A recent Ethiopian immigrant to Israel presented with pneumococcal sepsis, massive splenomegaly and lymph-adenopathy. Investigations revealed many features of both hairy cell leukaemia (HCL) and hyperreactive malarious splenomegaly (HMS). Proguanil therapy for HMS was followed by rapid, marked decrease in spleen size, disappearance of the tartrate-resistant acid phosphatase-positive cells characteristic of HCL, and increasing eosinophilia, but unchanged lymphadenopathy.
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PMID:Massive splenomegaly responsive to proguanil and with features of hairy cell leukaemia. 777 47

Acid phosphatase (AcP, EC 3.1.3.2) is represented by a number of enzymes that can be differentiated according to structural and immunological properties, tissue distribution, subcellular location and other features; these AcP isoenzymes share similar catalytic activity toward phosphoesters in an acidic medium. Classically, AcPs have been divided into four types according to their sensitivity to tartrate and to their origin: erythrocytic, lysosomal, prostatic AcP, and an AcP enzyme that was first identified in hairy cell leukemia (HCL). This latter AcP was termed isoenzyme 5 (based on its electrophoretic mobility) or human type 5, tartrate-resistant acid phosphatase (TRAP). Differences in various physicochemical properties, lack of amino acid sequence similarity and different chromosomal locations of the respective genes showed that the four AcP isoenzymes are not related. The biochemical properties of TRAP are unique: resistance to inhibition by tartrate, but inhibition by molybdate; glycoprotein of 30-40 kDa occurring as two similar isoforms with different carbohydrate content, each composed of dissimilar subunits of 16 and 23 kDa in disulfide linkage; active at acid pH (optimum at 5-6) with basic pI (8.5-9.0); presence of an iron active site giving the purified protein a purple color. The TRAPs of different human sources (HCL spleen, osteoclastoma, Gaucher's spleen, placenta) have an 85-94% homology in their amino acid sequences. Full-length TRAP cDNAs (1.4 kb) have been cloned from human placenta and Gaucher's spleen. Variations in TRAP structure appear to result from post-translational modifications and not from the existence of a multigene family as only a single TRAP gene and a single mRNA species have been reported. This notion of a single TRAP gene is supported by the substantial sequence homology found among the various TRAPs from human tissues and from animal sources (e.g. bovine spleen and bone; rat spleen, bone and epidermis; pig uterus). The latter enzyme preparations of animal origin have been described for many years as the purple acid phosphatase (PAP). However, the high degree of sequence homology indicated that TRAP and PAP enzymes represent a single entity belonging to the class of metalloproteins. The human TRAP gene was assigned to chromosome 15 and to chromosome 19 by two groups. TRAP protein is localized in lysosomes or similar organelles and is not secreted. The serum level of TRAP was found to be increased during physiological bone growth, in Gaucher's disease, and in malignancies metastasized to bone (resulting from increased osteoclastic activity).(ABSTRACT TRUNCATED AT 400 WORDS)
Leukemia 1994 Mar
PMID:Characterization and expression of tartrate-resistant acid phosphatase (TRAP) in hematopoietic cells. 812 41

Tartrate-resistant acid phosphatase (TRAP) was first identified in cells from patients with hairy cell leukaemia. Subsequently, it has been found in other leukaemias, B-lymphoblastoid cell lines, osteoclasts and subsets of normal lymphocytes, macrophages, and granulocytes. Recent data indicate that TRAP and porcine uteroferrin, a placental iron-transport protein, represent a single gene product. However, the intracellular role of TRAP is unknown. We used a full-length human placental TRAP cDNA probe to examine TRAP expression in human peripheral mononuclear cells (PMCs). TRAP mRNA increased 50-75-fold after 24 h in unstimulated PMC cultures. Cell-fractionation experiments indicated that monocytes were the main cell population accounting for increased TRAP mRNA transcripts, and this was confirmed by histochemical staining for TRAP enzyme activity. Because expression of other iron-binding and -transport proteins is controlled by iron availability, we examined the role of iron in regulating TRAP expression. Increase of TRAP mRNA transcripts in PMCs was inhibited by 50 microM desferrioxamine, a potent iron chelator. The 5' flanking region of the TRAP gene was cloned from a mouse genomic library. In preliminary transient transfection experiments, it was determined that the 5'-flanking region of the TRAP gene contained iron-responsive elements. Therefore, a series of stably transfected HRE H9 cell lines was developed bearing genetic constructs containing various segments of the murine TRAP 5' promoter region driving a luciferase reporter gene. Treatment of transfectants with 100 micrograms/ml iron-saturated human transferrin (FeTF) was performed to assess iron responsiveness of the constructs. Constructs containing a full-length TRAP promoter (comprising base pairs -1846 to +2) responded to FeTF with a 4-5-fold increase of luciferase activity whereas constructs containing only base pairs -363 to +2 of the TRAP promoter did not respond. Constructs containing 1240 or 881 bp of the TRAP promoter gave only a 1.5- to 2-fold increase of luciferase activity with FeTF. In all cases, increase of luciferase activity was blocked by desferrioxamine. Cells transfected with another luciferase construct driven by a simian virus 40 promoter did not show any increase of luciferase activity with FeTF. These data indicate that expression of TRAP is regulated by iron and that this regulation is exerted at the level of gene transcription. The transfection experiments also suggest that the region of the TRAP 5'-flanking sequence between base pairs -1846 and -1240 contains an iron regulatory element.
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PMID:Transcriptional regulation of the tartrate-resistant acid phosphatase (TRAP) gene by iron. 813 51

Certain osteoclastic markers (multinucleation and tartrate-resistant acid phosphatase) were induced in human leukemia HL-60 cells by treatment with 10(-7) M 1,25-dihydroxy-vitamin D3 [1,25(OH)2D3] for 10 days. However, no formation of pits on a bone substrate by vitamin-treated HL-60 cells was detected. Expression of calcitonin receptors (CTR), another osteoclastic marker, was examined by means of the reverse transcriptase polymerase chain reaction. The human CTR-cDNA (T47D isotype) was amplified from untreated HL-60 cells, but not from cells treated with 1,25(OH)2D3. The CTR mRNA disappeared within 24 h after the treatment. Thus, 1,25(OH)2D3-differentiated HL-60 cells failed to show two intrinsic characteristics of osteoclasts, pit formation on a bone substrate and expression of CTR. We then examined the expression of CTR on established human leukemia cell lines. The CTR mRNA was expressed in myeloblastic ML-1 and promyelocytic HL-60 leukemia cells but not in more mature macrophage-like cell lines, U-937 and THP-1 cells. Neither B cell leukemia BALL-1, T cell leukemia Jurkat, promegakaryoblastic leukemia Meg-J, nor cervix uteri carcinoma HeLa S3 cells amplified the CTR products. The cDNA of BIN67-isotype CTR, that has an additional 16-amino acid insert in the putative first intracellular loop of T47D-type CTR [Kuestner et al. (1994) Mol. Pharmacol. 46, 246-255], was amplified by neither strain tested. It was suggested that the T47D-type CTR is a novel differentiation antigen of immature myeloid lineage cells.
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PMID:Expression of calcitonin receptors on human myeloid leukemia cells. 854 84

The expression and protein structure of the tartrate-resistant acid phosphatase (TRAP), an iron-containing lysosomal glycoprotein in cells of the mononuclear phagocyte system, have been analyzed extensively in the past. In some diseases, like hairy cell leukemia and Gaucher's disease, cytochemically detected TRAP expression is used as a disease-associated marker. In this paper we describe the isolation of a genomic cosmid clone of the human TRAP gene. Restriction mapping revealed a 22-kb insert and the complete genomic structure of the TRAP gene. A 6-kb HindIII-fragment harboring the entire TRAP gene was subcloned and the 5'-flanking region of 3026 bp was sequenced. Analysis of the sequence data showed the presence of potential transcription factor binding sites. Two transcriptional start sites were identified in the untranslated exon 1 at positions -349 and -347 bp relative to the translational start codon. Linked to a luciferase-encoding reporter gene the 5'-flanking region was sufficient to direct transcription in the heterologous cell line BHK-21. Treatment of the transfected cells with different modulators of the intracellular iron content showed that regulation of TRAP expression is dependent on iron. In summary, these data imply a possible functional role of the TRAP gene product either in the storage or the transport of iron.
Leukemia 1996 Apr
PMID:Cloning and characterization of the human tartrate-resistant acid phosphatase (TRAP) gene. 861 40

Tartrate-resistant acid phosphatase is an inducible marker of cell differentiation and activation expressed by specialized cells of macrophage lineage and some activated lymphocytes. Clinically, this phosphatase is a diagnostic marker for hairy cell leukaemia and osteoclast activity. The cDNA for this enzyme has been cloned from a placental expression library, yet the cell(s) expressing the enzyme protein has not been determined with certainty. Our laboratories have developed a monoclonal antibody, 9C5, suitable for immunohistochemical localization of tartrate-resistant acid phosphatase in paraffin sections. The purpose of this study was to use antibody 9C5 to identify cells expressing tartrate-resistant acid phosphatase in sections of paraffin-embedded, normal, full-term placenta and to determine if those cells expressed other macrophage markers including CD68 (PG-M1 antibody), LN5, lysozyme, alpha 1-antitrypsin and alpha 1-antichymotrypsin. Histochemical localization of activity in frozen sections was compared with immunohistochemical localization in paraffin sections of the same tissue specimens. The activity and antigenicity of this enzyme were detected in decidual cells, syncytiotrophoblast, and some macrophages distributed throughout maternal and embryonic tissues, but not in neutrophils. Unlike other tissues previously examined, placenta contains significant numbers of the phosphate-positive cells that are not of macrophage origin.
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PMID:Localization of tartrate-resistant acid phosphatase in human placenta. 873 86

Polyclonal B lymphocytosis was found in four patients having clinical and hematologic features resembling those of hairy cell leukemia (HCL). All four patients were women between 37 and 67 years of age. Three patients had splenomegaly. Lymphadenopthy was absent or slight. Persistent lymphocytosis was seen in all the patients, and anemia and/or thrombopenia was observed in three of the patients. Abnormal lymphocytes have long microvilli and prominent membranous ruffles on their surfaces. Bone marrow aspirates and biopsy specimens showed increased numbers of abnormal lymphocytes with round nuclei and abundant pale cytoplasm. Although these findings were similar to those of HCL, studies of Ig gene rearrangements and expression showed the polyclonal proliferation of B cells. We called this new disease hairy B-cell lymphoproliferative disorder (HBLD). All four patients exhibited a polyclonal increase in serum IgG. The morphology of the cells in HBLD was more similar to that of leukemia cells of a variant form of HCL (HCL-Japanese variant) than to typical HCL cells. The surface IgG+, CD5-, CD11c+, CD22+, CD24-, CD25- phenotype and the weak tartrate-resistant acid phosphatase activity in the cells were identical to those of HCL cells of the Japanese variant. Our findings suggest that the B cells in HBLD are the nonmalignant counterpart of leukemic B cells in HCL-Japanese variant.
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PMID:Polyclonal B-cell lymphocytosis with features resembling hairy cell leukemia-Japanese variant. 929 52

To determine the influence of polymethylmethacrylate (PMMA) wear particles on macrophage-osteoclast differentiation, PMMA particles were added to mouse monocytes which were cocultured with UMR 106 osteoblast-like cells in the presence of 1,25 dihydroxy vitamin D3[1,25(OH)2D3] for up to 7 days on glass coverslips and for up to 14 days on human cortical bone slices. An increase in osteoclast differentiation, as evidenced by the expression of the osteoclast-associated enzyme tartrate-resistant acid phosphatase (TRAP) and the extent of lacunar bone resorption, was observed in monocyte cultures to which PMMA had been added. Interleukin 4 (IL-4) and Leukemia Inhibitory Factor (LIF) added to these cocultures caused considerably less expression of TRAP and significant inhibition of lacunar bone resorption. This inhibitory effect was reversed by the addition of specific neutralizing antibodies to LIF and IL-4. These findings show that PMMA-wear particle-associated macrophages exhibit an enhanced capacity for differentiation to osteoclastic bone-resorbing cells.
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PMID:Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor. 906 74

Inflammatory processes are mediated by many cellular events involving different cell types (leukocytes, monocytes, stromal cells, etc.). Numerous soluble mediators regulate these reactions, including leukaemia inhibitory factor (LIF), a cytokine which may play an important role in inducing acute-phase protein synthesis by hepatocytes during inflammation. This study was designed to determine the effects of LIF on the human monocyte/macrophage lineage and provide a better definition of its behaviour during systemic inflammation. In-vitro exposure of human long-term bone marrow cultures to recombinant human LIF significantly increased (about two-fold) the number of multinucleated cells (MNC) formed after three weeks of culture. These LIF-induced MNC expressed tartrate-resistant acid phosphatase, and LIF increased this intracellular activity by about 50%. MNC displayed phagocytotic activity but were unable to degrade sperm whale dentin or respond to human calcitonin. They did not possess the main characteristics of osteoclasts and were in fact macrophage polykaryons. Our results demonstrate for the first time that LIF can induce macrophage polykaryon formation from human bone marrow culture, suggesting that this factor not only produces leukocytes but also has a direct influence on the monocyte/macrophage lineage.
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PMID:Upmodulation of multinucleated cell formation in long-term human bone marrow cultures by leukaemia inhibitory factor (LIF). 906 95


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