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)

Enzymatically homogeneous populations of lymphocytes, monocytes, and neutrophils were isolated by zonal centrifugation from 5 untreated patients with chronic lymphocytic leukemia (CLL) and 2 patients with CLL in full remission. The cells were then quantitatively analyzed for six leukocytic enzymes and compared with cells from normal subjects. CLL monocytes were deficient in beta-glucuronidase (0.06 units; normal, 0.16), myeloperoxidase (0.07 mg; normal, 0.5 mg), and lysozyme (0.7 mg; normal, 3.3 mg). In 2 cases, CLL neutrophils were severely deficient in lysozyme (1 to 2 mg; normal, 7 mg) and myeloperoxidase (2 to 3 mg; normal, 7 mg). Neutrophil alkaline phosphatase and neutral protease were unaffected. CLL lymphocytes shared with the monocytes the deficiency of beta-glucuronidase (0.03 units; normal, 0.09 units). The 2 CLL patients in full remission carried normal enzyme levels in leukocytes of all three cell lines. The CLL lymphocytes of untreated patients were unresponsive to mitogens but became responsive in remission. The CLL monocytes from both untreated and treated patients transformed into macrophages. The pattern of shared enzyme deficiency among lymphocytes, monocytes, and neutrophils of CLL patients and its normalization in all three cell types under remission suggest that the differentiation of the three leukocytic cell lines may be an enzymatically interlinked process and that the deficiency of these enzymes in leukemia may reflect an interrelated aberrant differentiation of the leukemic cells.
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PMID:Monocyte and granulocyte defect in chronic lymphocytic leukemia. 21 99

Heterogeneous clinical features of inherited hemolytic anemia due to pyruvate kinase (PK) deficiency were observed in three related homozygous patients. Erythrocytes were separated into old and young cells by means of density-layer centrifugation using a new supporting medium: Stractan-Urografin gradients. Those fractions containing older RBC disclosed defective PK which resulted in an impaired metabolism. Following an intake of chloramphenicol the clinical course of one female family member converted to acute monocytic leukemia. Thus, the report of a PK instability trait, in one family member associated with pancytopenia which converted in leukemia, suggests that inherited red cell enzyme deficiency might be also an expression of the vulnerability of the hematopoietic stem cells.
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PMID:[Inherited hemolytic anemia due to pyruvate kinase deficiency: II. Density-layer centrifugation of erythrocytes (author's transl)]. 28 28

The case of a 27-year-old woman with pancytopenia, revealing acute monocytic leukaemia and haemolytic anaemia, is described in detail. The underlying cause for the red cell destruction was found to be a pyruvate kinase (PK) instability. Further investigation into three generations of her family (n = 12) disclosed a hereditary PK instability. This was proven by performing biochemical studies to elucidate mutants representing a structurally defective enzyme. Since conversions of pancytopenia with acquired red cell enzyme deficiency into leukaemia have been described, our observation emphasizes that hereditary red cell enzymopathy might also be associated with adult acute leukaemia.
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PMID:Haemolytic anaemia with hereditary pyruvate kinase instability developing acute leukaemia. 105 38

A 19 year old woman presented as a case of haemolytic anaemia due to multi-enzyme deficiency of the erythrocyte. After a transient improvement with folic acid therapy, she developed acute myeloblastic leukaemia. This is the second reported case of a myelodysplastic syndrome presenting with a haemolytic picture and subsequently developing an acute myeloblastic leukaemia.
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PMID:A case of pre-leukaemia masquerading as haemolytic anaemia due to multi-enzymopathy of the red cell. 276 72

Adult T-cell leukemia (ATL) is a retrovirus-associated leukemia with poor prognosis and often has deletions of the p16INK4a and p15INK4b genes on chromosome 9p21. The gene for methylthioadenosine phosphorylase (MTAP), a purine and methionine metabolic enzyme, resides approximately 100 Kb telomeric to the p16INK4a gene and is frequently co-deleted with the tumor suppressor gene in a variety of cancers. This enzyme deficiency can be exploited for selective chemotherapy with de novo purine synthesis inhibitors and/or methionine depletion. To determine whether ATL can be a candidate for selective chemotherapy based on genetic alterations on chromosome 9p21, we analyzed the MTAP gene in 41 samples from ATL patients (27 acute type and 14 chronic type ATL) and 3 cell lines established from ATL patients. Five samples from the acute type had deletions of the MTAP gene (4 total deletions and 1 partial deletion of exons 6-8). The MTAP gene was always co-deleted with p16INK4a. No deletion of the MTAP gene was detected in samples from the chronic type. Of 3 cell lines, 2 showed partial deletions of exons 5-8 of the MTAP gene, and 1 lost all exons. The p16INK4a gene was deleted in all cell lines. In conclusion, deletions of the MTAP gene were found in 5 of 27 acute type ATL samples. Acute type ATL with MTAP deficiency can be a good candidate for selective chemotherapy by depleting purines and/or methionine.
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PMID:The methylthioadenosine phosphorylase gene is frequently co-deleted with the p16INK4a gene in acute type adult T-cell leukemia. 942 90

Polyagglutination is the term applied to red blood cells (RBCs) that are agglutinated by almost all samples of human sera from adults but not by autologous serum or sera of newborns. The polyagglutinable state may be transient or persistent. Transient polyagglutinability results from the exposure of normally cryptic antigens by bacterial enzymatic activity during the course of an infectious process. RBCs are polyagglutinable because most sera from adults contain agglutinins for the exposed antigens. This type of polyagglutination can often be reproduced in vitro with bacterial culture fluids or isolated enzymes. Persistent polyagglutination may be a consequence of somatic mutation leading to a cellular lineage characterized by an enzyme deficiency that results in exposure of a normally cryptic antigen, Tn. Most human sera contain anti-Tn. Tn polyagglutination is regularly accompanied by leukopenia and thrombocytopenia and has been associated with leukemia. Other forms of persistent polyagglutination are due to the inheritance of rare blood groups or are associated with a hematologic dyscrasia.
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PMID:Red blood cell polyagglutination: clinical aspects. 1079 87

Methylthioadenosine phosphorylase (MTAP) involved in the metabolism of purine and polyamine has been known to be deficient in a variety of tumors. Although this enzyme deficiency was reportedly caused by partial or total deletion of the MTAP gene, human MTAP-deficient lymphoma cell line DHL-9 has the intact MTAP gene. In order to determine the mechanism of MTAP deficiency in DHL-9, we carried out methylation-specific PCR analysis of sodium bisulfite-treated genomic DNA followed by DNA sequence analysis. Following incubation with various concentrations of 5-Aza-2'-deoxycytidine, DHL-9 cells were subjected to RT-PCR and an immunoblot analysis for MTAP expression. MTAP promoter in DHL-9 cells was methylated at cytosine of all CpG dinucleotides analyzed. Moreover, 5-Aza-2'-deoxycytidine treatment induced DHL-9 cells to express MTAP mRNA and protein. Taken together, MTAP deficiency in DHL-9 was caused by transcriptional silencing due to promoter methylation. Promoter methylation of the MTAP gene was also found in DNA samples from adult T-cell leukemia patients. These results indicated that promoter hypermethylation is another mechanism of MTAP deficiency in human malignancy. Thus, immunological diagnostics will be needed for an accurate evaluation of MTAP expression at the protein level.
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PMID:Methylthioadenosine phosphorylase gene is silenced by promoter hypermethylation in human lymphoma cell line DHL-9: another mechanism of enzyme deficiency. 1575 93

Over the last five years significant progress has been made towards the transfer of foreign genetic material to eukaryotic cells. The eventual aim to devise novel therapeutic strategies to treat human diseases, in particular solid tumours and monogenic disorders associated with various enzyme deficiency states. The easy accessibility and the ability of haemopoetic stem cells to self replicate and repopulate makes them desirable targets for gene transfer. In theory the introduction of a small number of gene modifed haemopoetic progenitor cells can allow therapy of an individual for life without any further intervention. This approach has been used for the treatment of single gene defects such as ADA deficiency. Furthermore, gene transfer technology has increasingly been exploited for bone marrow and peripheral blood stem cell marking studies, modification of cell sensitivity to cytotoxic drugs and the genetic modification of leukemic cells with the intention of inducing a leukemia specific cytotoxic T cell response. Vector development is of crucial importance for the successful delivery of genes in haemopoetic stem cells and leukemia cells. The objective of this review is to discuss in detail the properties of current vector technology that are pertinent to haemopoietic cell gene transduction.
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PMID:The Scope of Viral Vectors for the Transduction of Haemopoietic Cells. 2741 82