Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The first part of the paper outlines the actual situation of the recent investigations on the interpretative problem of the immunological deficits combined with enzymatic deficits. ADA deficit associated with combined immunodeficiency is an autosomal recessive form. Low enzyme levels, which is produced by a structural gene located on chromosome 20, were detected in chronic lymphatic leukemias where ADA decrease is correlated to low levels of T lymphocytes and the prevalence of an atypical B lymphocyte population. Particularly high levels of ADA were detected in acute lymphoblastic leukemias, in transplant rejection, in blastic crisis of chronic myeloid leukemia... NP deficit is associated with a T branch immunodeficiency, with high levels of inosine, guanosine, hypouricemia, hypochromic microcythemia and hematopoietic tissue megaloblastosis. This enzyme, with trimeric structure, whose structural gene is located on chromosome 14, shows a cytoplasmic location, and its maximum activity is to be found in T lymphocytes separated by rosetting. IGPT deficit is to be held responsible for the neurological Lesch-Nyhan syndrome. This deficit is associated with a depression of B lymphocyte function evaluated as response to the mitogens (PWM, Protein A) or as specific immunoglobulins production. At last the Authors report some personal investigations performed on hemolysates and lymphocytes of subjects with impaired immunity, as well as on some children at birth to establish the correlation between ADA and NP behaviour and immunosurveillance. Lastly, the data on the variations of the enzymatic and immunological parameters of subjects with immunodeficiency associated to enzymopenia after red cell transfusion are reported.
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PMID:[Immunodeficiencies and enzyme deficiencies]. 10 63

In order to determine the incidence and causes of death during the first 100 days after BMT (early deaths) in a pediatric population we have examined data reported in the AIEOP BMT Registry. Up to July 1990, data on 486 children who underwent allogeneic (180) or autologous (306) BMT were evaluable. The children had acute lymphoblastic leukemia (148 cases), acute non-lymphoblastic leukemia (127 cases), neuroblastoma (82 cases), chronic myelogenous leukemia (15 cases), aplastic anemia (nine cases), solid tumors, lymphoma, immunodeficiency or storage diseases. The overall survival is 55% for allogeneic HLA matched and 38% for autologous transplants at 5 years, 24% for HLA mismatched graft at 2 years. Out of the 486 children, 70 (14%) died during the first 100 days after BMT: 33/306 (11%) after autologous BMT, 24/150 (16%) after allogeneic matched BMT and 13/30 (43%) after mismatched BMT. Causes of early death were as follows: disease progression: 12 children (10/306 after autologous and 2/180 after allogeneic BMT); infection: 12 children (five after autologous and seven after allogeneic BMT); interstitial pneumonitis: 21 children (seven after autologous and 14 after allogeneic BMT); cardiac failure: five children (four after autologous BMT); veno-occlusive disease: eight children (three after autologous, five after allogeneic BMT); acute renal failure: three children (one after autologous and two after allogeneic BMT); multiple organ failure: two cases (one after autologous BMT); cerebral hemorrhage: three children (one after autologous BMT); hypertension: one child; acute GVHD: three children (12% of early deaths after allogeneic BMT).
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PMID:Early deaths in children after BMT. Bone Marrow Transplantation Group of the Italian Association for Pediatric Hematology and Oncology (AIEOP) and Gruppo Italiano Trapianto di Midollo Osseo (GITMO). 146 3

This study examined the safety and pharmacokinetic profile of a potentially therapeutic and fully human anti-CMV monoclonal antibody (SDZ MSL-109) in a phase I dose escalation trial in patients receiving allogeneic bone marrow transplants. Fifteen adult marrow transplant patients, twelve with chronic myelogenous leukemia and three with acute nonlymphocytic leukemia, in cohorts of five patients each, were administered monoclonal antibody intravenously at doses of 50, 250, and 500 micrograms/kg at approximately three-week intervals for six months. Administration of the monoclonal antibody was associated with minimal side effects and no dose-related toxicity. Antibody elimination curves in all dose groups were consistent with a two-compartment model with an alpha half-life at the low, middle, and high dose groups of 1.03, 0.82, and 0.79 days, and a beta half life of 13.9, 14.0, and 16.5 days, respectively. The volume of distribution decreased with repetitive dosing to approximate the plasma volume in each patient and the pharmacokinetic profile was comparable to that of human IgG. There was no host antiidiotypic or antiallotypic antibody formation, indicating that MSL-109 was not immunogenic. Further studies are warranted to assess the potential efficacy of human monoclonal anti-CMV disease in marrow transplant recipients and other patients with immunodeficiency disorders.
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PMID:Phase I study of safety and pharmacokinetics of a human anticytomegalovirus monoclonal antibody in allogeneic bone marrow transplant recipients. 164 4

Even though they possess normal to increased numbers of circulating natural killer (NK) cells, patients with chronic myelogenous leukemia (CML) have a functional NK-cell deficiency which is restorable in vitro in the presence of recombinant IL-2. We therefore measured the level of IL-2 production by both T-helper and NK cells from CML patients as compared to normal controls using PHA-stimulated peripheral blood mononuclear cells (PBMs) as well as FACS-sorted CD4+ (OKT4+) lymphoid cells and FACS-sorted CD16+ (B73.1+) lymphoid cells. Peripheral blood mononuclear cells from CML patients demonstrated markedly defective IL-2 production as compared to normal controls (4.0 +/- 1.6 and 5.9 +/- 1.4 units/ml after 24 hr of 5 and 10 micrograms/ml PHA stimulation as compared with 40.7 +/- 10.3 and 69.3 +/- 15.1 units/ml for normal subjects). In addition to the decreased relative percentage of CD4+ (OKT4+) lymphoid cells in CML patients, FACS-sorted CD4+ (OKT4+) cells also demonstrated a significant defect in IL-2 production, (10.8 +/- 3.6 units/ml as compared to 39.0 +/- 5.8 units/ml after 24 hr stimulation with 10 micrograms/ml PHA). FACS-sorted CD16+ (B73.1+) lymphoid cells from CML patients also demonstrated significantly decreased IL-2 production after 24 hr incubation with increasing concentrations of PHA or with the NK-sensitive target K562 as compared to normal controls. Defective IL-2 production by PBMs, CD4+ (OKT4+), and CD16+ (B73.1+) cells from CML patients was also evident after 48 hr of PHA stimulation. Although the percentages of both T4+2H4+ and T4+4B4+ subsets are significantly decreased in CML patients, CML patients have normal ratios of T4+4B4+/T4+2H4+ subsets as compared to normal controls. These and previous results support the hypothesis that decreased IL-2 production by both T-helper and NK cells from CML patients may be mechanistically related to the observed NK-cell immunodeficiency in CML patients.
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PMID:Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. III. Defective interleukin-2 production by T-helper and natural killer cells. 252 12

An increasing number of diseases may be treated successfully by allogeneic bone marrow transplantation (BMT). Initially used for the treatment of immunodeficiency where a cell series or product is replaced, it has now become routine treatment for many forms of leukemia where the transplant provides the rescue after lethal marrow ablation. Recently, diseases such as thalassemia and other inherited metabolic diseases have also been treated by BMT. Formerly the problems of BMT were mainly concerned with graft versus host disease (GVHD) in HLA-matched transplants with HLA-mismatched ones not being possible as GVHD was usually fatal. Since the development of techniques for T cell removal the incidence of GVHD has greatly diminished. T cell removal has also allowed HLA haploidentical mismatched grafts to be performed successfully for immunodeficiency, but there is still a high graft rejection rate in leukemia. This also occurs to a lesser extent with HLA-matched grafts in leukemia. Furthermore, in certain forms of leukemia, particularly chronic granulocytic leukemia, the relapse rate after T cell-depleted BMT is much higher. Trials of better forms of bone marrow conditioning of the recipient are being attempted in order to prevent graft rejection and leukemia relapse. These include total lymphoid irradiation, heavier irradiation and chemotherapeutic regimens, or the use of in vivo monoclonal antibodies such as CAMPATH 1G or anti-LFA-1 (CD11a). In the future, positive selection of stem cells combined with hemopoietic growth factors may allow engraftment without graft versus host disease. This should become the method of choice for autologous transplantation for malignancy. Two monoclonal antibodies directed against the human progenitor cell antigen 1 (HPCA-1) (CD34) have been used for autologous positive stem cell selection in primates and these cells gave full hemopoietic reconstitution in the animals following lethal total body irradiation.
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PMID:Recent advances in bone marrow transplantation. 256 39

The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.
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PMID:Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation. 304 69

A new case of Campylobacter hyointestinalis-associated diarrhea in a human is reported. The medical history of the patient was significant for immunodeficiency because of an evolutive chronic myeloid leukemia. The diarrhea rapidly stopped after administration of oral erythromycin. No other enteropathogenic agent was found by routine examination of stools. Although neither serology nor autopsy was available, this observation appears to be suggestive of the possible enteropathogenicity of C. hyointestinalis for patients at risk.
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PMID:Campylobacter hyointestinalis: an opportunistic enteropathogen? 323 Jan 40

The populations of lymphocytes and serum immunoglobulins were explored in 20 patients with erythremia, 26 patients with sub-leukemic myelosis, 38 patients with pronounced chronic myeloid leukemia, and 33 patients with the blastic phase of the illness. The patients with chronic myeloproliferative diseases manifested cellular immunodeficiency that was aggravated as the disease progressed. In the pronounced stage, the patients showed relative preservation of humoral immunity whereas in the terminal stage they developed humoral deficiency. Study of the time-course of changes in the immunological characteristics has demonstrated that deterioration of the characteristics starts during blast transformation of myeloproliferative diseases. This may serve as a criterion for predicting exacerbations and early diagnosis of the blastic phase.
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PMID:[Indices of cellular and humoral immunity in chronic myeloproliferative diseases]. 349 38

Impairment in T cell proliferation in response to E. coli and in CML to unrelated alloantigens was usually observed in patients early after marrow grafting and persisted in long-term patients with chronic GVHD but not in those without chronic GVHD. We analyzed various cellular functions in the pathway of T cell activation and found that in patients with immunodeficiency, (1) their M phi usually could process and present antigens to normal T cells, (2) their T cells did not proliferate even in the presence of normal antigen-pulsed M phi, (3) IL-2 production by T cells was deficient, and (4) exogenous IL-2 restored CML activity in cells of most patients early after grafting but not in cells of most patients with chronic GVHD. Therefore, failure to induce proliferation and cytotoxicity in T cells of marrow recipients is not likely due to M phi defects but because of ineffective communication among T cell subsets, probably related to impaired IL-2 production and/or unresponsiveness to IL-2.
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PMID:Ineffective cellular interaction and interleukin 2 deficiency causing T cell defects in human allogeneic marrow recipients early after grafting and in those with chronic graft-versus-host disease. 639 Aug 48

Genetic factors suspected in the etiology of human hemopoietic neoplasia, such as leukemia, lymphoma and multiple myeloma, are reviewed. High incidence of consanguineous marriage was found in parents of familial leukemia in siblings. It was also noted that the age of patients with familial leukemia in children of consanguineous parents was younger than that of cases whose parents were not related. These findings suggest that genetic factors may play an important role in the etiology of familial leukemia in siblings. According to the frequencies of familial aggregations in close relatives, the genetic relationships were supposed to be important in chronic lymphocytic leukemia and acute leukemia, but not in chronic granulocytic leukemia. Increased prevalence of autoimmune diseases in relatives of leukemic patients suggests a possibility of genetic immunodeficiency as a common etiologic factor in both diseases. Immunodeficiency was found in unaffected relatives of patients with familial leukemia and lymphoma. Genetic factors were also suggested by the familial occurrences of multiple myeloma and primary macroglobulinemia, and the incidence of benign monoclonal gammopathy in relatives of patients with these diseases. HLA studies revealed the increased frequencies of A2 in acute lymphocytic leukemia, of B5 and B18 in Hodgkin's disease, and of A5 and B18 in multiple myeloma. From such relationships existing between familial immunodeficiencies and hemopoietic neoplasia, genes regulating the immune responsiveness might be involved in susceptibility to these diseases.
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PMID:[Genetics and hemopoietic neoplasia]. 718 26


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