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)

Cell membrane components that contain beta 2-microglobulin were purified from cells of a human T cell-type leukemia cell line, HPB-ALL. They contained membrane components that have the same molecular size and the same subunit structure as HLA(A,B,C) antigens but are separable from the typical beta 2-microglobulin-containing cell membrane components, i.e., the HLA (A,B,C) antigens, by xenoantibody reagents. A sensitive radioimmunoassay was constructed for detection of the T cell membrane components. The assay revealed that the cell membrane components are expressed exclusively on cells of T cell-type leukemia cell lines among the human lymphoid cell lines tested, predominantly in thymus, among the human organs and tissues tested. They were not present on cells of human B cell-type cell lines or on cells of nonlymphoid organs and tissues. No alloantibodies directed to the T cell membrane components, the putative human homologues of mouse TL antigens, were found in any of the human tissue typing sera tested.
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PMID:Human cell membrane components dominant in T cell lineage: identification and characterization of human TL-like antigens. 38 77

Correlation between some histocompatible antigens and leukemia has been described both in men and in experimental animals. In 1970 Walford found an exceptionally high association between the illness and antigens of the HLA system in children with acute leukemia who had long life duration. It is therefore supposed that these antigens should not be associated with predispositional factors of the illness, instead, they are more likely to have influence over the course of the illness itself. Consequently, the authors have examined 15 children of various age who had acute leukemia. All children were examined for all antigens of the first and second HLA system, as well as for ABO and Rh genotype. The patients' blood was also checked for existence of cytotoxic antigens. Frequency of certain antigens and haplotypes was found in both children and their parents so that a comparison with antigen and haplotype frequency was also made.
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PMID:[Analysis the incidence of HL-A-system antigen incidence in children treated for acute lymphoblastic leukemia]. 41 81

HLA phenotypes of 13 patients surviving in lasting first remission over 6 years after BCG immunotherapy for acute childhood lymphoblastic leukaemia (ALL) were compared to phenotypes of normal subjects and of surviving ALL patients treated exclusively with chemotherapy. Among the BCG-treated patients, the frequency of the antigen HLA-BW 17 was 46.1% vs 7.3% in healthy controls (p less than 0.001) and the frequency of the antigen HLA-AW 33 was 30.8% vs 1.2% (p less than 0.001). 9 patients possessed at least one of these two antigens (69.2% vs 8% in controls p less than 0.001). Phenotypes of the chemotherapy-treated patients did not differ significantly from controls. These results suggest the existence in humans of HLA-linked genes which are involved in the response to BCG immunotherapy in ALL.
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PMID:[HLA phenotypes in patients surviving a long time after immunotherapy with BCG for acute childhood lymphoblastic leukemia. Arguments in favor of the existance of a gene for immune response in human leukemia]. 41 39

Since ten years, there is an extensive search for association between antigens of the major histocompatibility system HLA and malignant diseases. Data show only weak associations with Hodgkin disease and acute lymphocyte leukemia. For studies of a variety of solid tumours the difference between patients and controls do not attain statistical significance, except for nasopharyngeal carcinoma. According to the gene frequency variations in populations and the ethnic differences in some cancers, inter-population studies are possible. Significant geographic associations between some cancers and HLA antigens have been found. They give evidence for a genetic background of susceptibility or resistance to cancer.
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PMID:[HLA system and malignant diseases (author's transl)]. 66 76

Modifications of HLA antigens (transient loss or polyreactivity) were found in thirty-two of fifty-five examined patients with blood diseases (leukaemia, reticulosis, reticulo- and lymphosarcoma, lymphogranuloma, erythroblastoma) and malignant tumours. In two cases of acute myelosis transient alteration of HLA-A 2 antigen in HLA-A 28 was demonstrated. The relationship of HLA antigenic modification to chemotherapy was established, both by analysis of individual cases and by statistical evaluation of serological results in patients with or without chemotherapy (0-01 greater than P greater than 0-001). Chemotherapy is thus one of the causes for the development of HLA antigen modifications in blood diseases and malignant tumours.
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PMID:Chemotherapy--one of the causes of transient loss of HLA antigens and lymphocyte polyreactivity in patients with blood diseases and malignancies. 79 92

Remarkable differences were observed when 1,465 healthy Caucasian individuals and 128 healthy Negro individuals were compared for the genetic distribution of 25 different HLA antigens. Caucasians had a significantly higher frequency of A1, A3, B8, and Bw16, and Negroes of A28 and Aw30. The haplotype which had the highest incidence as well as the greatest positive linkage disequilibrium was A1-B8 among Caucasians and A2-B12 among Negroes. Genetic distance between the two races was 0.0592. The 89 Caucasian patients with renal failure did not demonstrate any significant deviations in phenotype frequencies (PF) of various antigens, when compared with healthy Caucasians; however, 48 similar Negro patients had twice as high an incidence of Bw17 as the healthy Negroes. No significant deviation in PF was observed in 77 Caucasian patients who had leukemia; however, 32 Caucasian patients who had back pain (24 also had back stiffness) due to spondylitic, arthritic or disc syndrome, had a significant increase of Bw16 and of B27, and a decrease of B12, when compared to Caucasian controls.
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PMID:The HLA polymorphism and susceptibility to disease. 96 89

Bone marrow transplantation from unrelated donors is being used increasingly for the treatment of patients with leukemia and several other hematologic disorders. Selection of unrelated bone marrow donors currently relies on serological HLA identity and negative mixed lymphocyte reactions between donor/recipient pairs. As serological HLA-DP typing is not feasible, we used the HLA-DPB1 oligonucleotide typing method to investigate whether the current selection procedure can guarantee complete MHC class II identity. In 40 consecutive patients, one third (62/193) serologically HLA-A, -B, -C, -DR and -DQ identical donors were found to be MLC-negative with a relative response below 5%. HLA-DPB1 oligonucleotide typing of these MLC-negative donors revealed that again only one third (20/62) was also identical for DP with their presumptive recipients. In the majority of pairs a disparity in graft-versus-host direction or in host-versus-graft direction of at least one allele was seen. These data indicate that, in spite of the strict MLC criteria used, the current procedure did not warrant complete MHC class II identity. This implies that oligotyping for DPB1 can improve matching and should be introduced for typing of volunteers.
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PMID:Selection of unrelated bone marrow donors: does the current procedure warrant complete MHC class II identity? 128 25

Crosslinking HLA-DR molecules by monoclonal antibodies (moAbs) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic calcium concentrations in activated human T cells. Binding of bacterial superantigens or moAbs to DR molecules on activated T cells was recently reported to induce homotypic aggregation through activation of protein kinase C (PKC) and mediated by CD11a/CD54 (LFA-1/CAM-1) adhesion molecules. Here, we report that moAbs directed against framework DR, but neither DR1, 2- and DRw52- nor DQ- and DP-specific moABs induced homotypic aggregation of antigen- and alloantigen-activated T cells, antigen-specific CD4+ T-cell lines, a CD8+ T-cytotoxic cell line, and T-leukemia cells (HUT78). Protein tyrosine kinase (PTK) inhibitor herbimycin A partly blocked class-II-induced aggregation responses. In contrast, phorbol ester (PMA)-induced aggregation was essentially unaffected. A potent inhibitor of PKC, staurosporin, inhibited both moAb- and PMA-induced aggregation responses. The aggregation responses were completely inhibited by low temperatures, cytochalasins B and E, and partly inhibited by EDTA and CD18 moAbs, but unaffected by aphidicolin, mitomycin C, an adenylate cyclase inhibitor (2'5'-dideoxyadenosine), and moAbs against other adhesion molecules (CD2/CD58 [LFA-3], CD28/CD28 ligand B7, CD4, and CD44). In conclusion, HLA class-II-induced aggregation responses in activated T cells appear to involve PTK and PKC activation and to be mediated through CD11a-dependent and independent adhesion pathways.
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PMID:Signal transduction by HLA class II molecules in human T cells: induction of LFA-1-dependent and independent adhesion. 128 78

The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.
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PMID:Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. 152 Aug 88

Cryopreserved human umbilical-cord (HUC) blood is an alternative to bone marrow as a source of haemopoietic "stem" cells for HLA-identical transplantation of children with leukaemia or Fanconi's anaemia. We have studied the in-vitro growth potential of HUC blood in clonogenic assays and in longterm haemopoietic cultures. Clonogenic assays showed that HUC blood produced as many haemopoietic-cell colonies as normal adult bone marrow and a higher proportion of primitive-cell colonies. In longterm culture on preformed irradiated marrow stroma, both progenitor-cell production and lifespan of cultures were significantly greater in HUC blood than in normal bone marrow (p = 0.0007). Our findings indicate that the quality and quantity of HUC-blood-derived haemopoietic "stem" cells are better than those of normal bone marrow. Therefore, single HUC-blood donations are probably sufficient for adults requiring transplantation for leukaemia and other haemopoietic disorders. Banking of HLA-typed HUC blood to facilitate transplantation of patients who lack a family donor should be considered.
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PMID:Growth of human umbilical-cord blood in longterm haemopoietic cultures. 136 Jan 7


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