Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This report describes an unusual clinical presentation of Li-Fraumeni syndrome. Family history revealed a mild aggregation of adult cancers in one generation, and an unusual clustering of brain tumours of early childhood in the following generation. In order to evaluate the genetic basis for cancer predisposition in this family, molecular genetic analysis for the occurrence of germline TP53 tumour suppressor gene mutations was performed on 12 siblings of two generations. Indirect mutation analysis was performed by the single-strand conformation polymorphism (SSCP) technique. Alterations were characterised by automated direct fluorescence sequencing analysis. Tumour material was also examined for p53 protein accumulation by immunohistochemistry. Initially, a TP53 gene germline missense mutation was detected in an 11-year-old kindred with acute myeloid leukaemia (AML) following intensive treatment of a brain tumour. In peripheral blood and bone marrow samples of this proband, a reduction to hemizygosity occurred. During AML treatment, detection of LOH of 17p was used as a marker for clonality and treatment control. The mutation was found to be inherited from the proband's mother, who was diagnosed with breast cancer at the age of 48 years. Further, three siblings were carriers, and two are apparently healthy at the age of 21 and 23 years. Knowledge of germline mutations may allow accurate DNA-based carrier diagnosis which is of important clinical significance for treatment strategy and control. Furthermore, the occurrence of unaffected carriers in this family raises questions about appropriate methods of cancer surveillance and counselling for these people.
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PMID:A new germline TP53 gene mutation in a family with Li-Fraumeni syndrome. 886

In this study we report 11 cases with chromosome abnormalities involving 3p21. Nine cases were diagnosed as myelodysplastic syndrome (MDS), and two as acute myeloid leukemia (AML). Six of nine MDS cases were secondary to a primary malignant disease. In two patients, AML was secondary to breast cancer and polycythemia vera (PV). Seven of eleven patients had a history of intensive polychemotherapy and/or radiation therapy for 3.5 to 5 years. The mean interval from initial therapy to secondary disease was 13.2 years. Complex chromosomal aberrations were found in all 11 cases. Band 3p21 was involved in translocations in 9 patients and in deletions in 2 patients. A t(3;16)(p21;p13) was found in two cases. Additional abnormalities frequently included a -5, -7, as well as deletions or rearrangements of these 2 chromosomes. Data reported in this paper suggest that 3p21 is a recurrent treatment-related breakpoint in MDS and AML and is likely to contain a gene involved in the pathogenesis of this disease.
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PMID:3p21 is a recurrent treatment-related breakpoint in myelodysplastic syndrome and acute myeloid leukemia. 897 89

Autologous bone marrow transplantation (ABMT) has considerably developed in the past 20 years. In AML, the beneficial role of purging the graft with cyclophosphamide derivatives (4-HC or mafosfamide) has been strongly suggested by retrospective studies from the European Cooperative Group for Blood and Marrow Transplantation and by single institution studies. Also, gene marking experiments have clearly shown that tumour cells infused with unpurged marrow indeed recirculate and in some instances, induce or contribute to tumour recurrence. Amifostine protects normal progenitor cells without concomitantly protecting colony forming unit leukaemic progenitors (CFUL). In comparative in vitro studies, we have shown that pre-incubation of normal marrow contaminated by leukaemic progenitors with amifostine followed by mafosfamide, results not only in a protection of the more mature progenitors (CFUGM, BFUE), but also sensitises leukaemic progenitors, so that in the end, the therapeutic index of mafosfamide is increasing by 6 logarithms. In the clinical field, it has been shown in patients with breast cancer autografted with protection by amifostine results in a shortening of the duration of aplasia of about 10 days. A European randomised study evaluating amifostine in the context of autografting for acute leukaemia has just started.
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PMID:The potential role of amifostine (Ethyol) in haematological malignancies. 897 20

Adoptive immunotherapy denotes the transfer of immunocompetent cells for the treatment of leukemia, cancer, or viral disease. It has regained much interest through the success of treating recurrent leukemia after allogeneic bone marrow transplantation with the transfusion of donor lymphocytes. Chimerism and transplantation tolerance toward the donor offer the possibility of adoptive immunotherapy using donor lymphocytes. In animal studies, donor lymphocytes could be transfused into the chimeric animal, if the transfusion was delayed after marrow transplantation. Transfused lymphocytes exhibit a graft-versus-leukemia effect and increase chimerism. Immunity could be transferred and immune reactivity toward new antigens improved. In human patients transfusion of donor lymphocytes was studied in leukemia recurring after marrow transplantation. It was very effective in the treatment of chronic myelogenous leukemia recurring after marrow transplantation. It was also effective in some patients with acute myeloid leukemia, myelodysplastic syndrome and myeloma; in acute lymphoblastic leukemia and lymphoma responses were rare. Responses in solid tumors as breast cancer have been described. Major complications are graft-versus-host disease and myelosuppression. Myelosuppression could be compensated by the transfusion of marrow. Graft-versus-host disease can be modified by the depletion of CD8-positive T cells from the lymphocyte concentrate or by transfusing very low numbers of cells and increasing doses in a stepwise fashion. The role of concomitant treatment with cytokines and activation of T cells by dendritic cells and vaccination remains to be defined.
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PMID:Adoptive immunotherapy with donor lymphocyte transfusions. 916 91

We have prospectively evaluated the feasibility and results of the biotin-avidin immunoadsorption method (Ceprate SC system) for a phase I/II study of T-cell depletion of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) for allogeneic transplantation. Twenty consecutive patients, median age, 40 years (21 to 54) and diagnoses of chronic myeloid leukemia in chronic phase (n = 5), acute myeloblastic leukemia (n = 7), acute lymphoblastic leukemia (n = 2), chronic myelomonocytic leukemia (n = 1), refractory anemia with excess of blasts in transformation (n = 3), histiocytosis X (n = 1), and chronic lymphocytic leukemia (n = 1), were conditioned with cyclophosphamide (120 mg/kg) and total body irradiation (13 Gy; 4 fractions). HLA identical sibling donors received G-CSF at 10 microg/kg/d subcutaneously (SC); on days 5 and 6 (19 cases) and days 5 to 8 (1 case) donors underwent 10 L leukapheresis. PBPC were purified by positive selection of CD34+ cells using immunoadsorption biotin-avidin method (Ceprate SC) and were infused in the patients as the sole source of progenitor cells. No growth factors were administered posttransplant. The median recovery of CD34+ cells after the procedure was of 65%. The median number of CD34+ cells infused in the patients was 2.9 (range, 1.5 to 8.6) x 10(6)/kg. The median number of CD3+ cells administered was 0.42 x 10(6)/kg (range, 0.1 to 2). All patients engrafted. Neutrophil counts >500 and >1,000/microL were achieved at a median of 14 days (range, 10 to 18) and 15 days (range, 11 to 27), respectively. Likewise, platelet counts >20,000 and >50,000/microL were observed at a median of 10 days (range, 6 to 23) and 17 days (range, 12 to 130), respectively. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine plus methylprednisolone. No patient developed either grade II to IV acute or extensive chronic GVHD. After a median follow-up of 7.5 months (range, 2 to 22) three patients have relapsed, and one of them is again in hematologic and cytogenetic remission after infusion of the donor lymphocytes. Two patients died in remission: one on day +109 of pulmonary aspergillosis and the other on day +251 of metastasic relapse of a previous breast cancer. Sixteen of the 20 patients are alive in remission after a median follow-up of 7.5 months (range, 2 to 22). In conclusion, despite the small number of patients and limited follow-up, it appears that this method allows a high CD34+ cell recovery from G-CSF mobilized PBPC and is associated with rapid engraftment without significant GVHD, and with low transplant related mortality.
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PMID:Rapid engraftment without significant graft-versus-host disease after allogeneic transplantation of CD34+ selected cells from peripheral blood. 916 34

Cigarette smoking has been clearly and unambiguously identified as a direct cause of cancers of the oral cavity, oesophagus, stomach, pancreas, larynx, lung, bladder, kidney and leukaemia, especially acute myeloid leukaemia. Additionally, cigarette smoking is a direct cause of ischaemic heart disease (the commonest cause of death in western countries), respiratory heart disease, aortic aneurysm, chronic obstructive lung disease, stroke, pneumonia and cirrhosis and cancer of the liver. Cigarette smoking can kill in 24 different ways and, although smoking protects against several fatal and non-fatal conditions, the adverse effect of smoking on health is largely negative. In developed countries as a whole, tobacco is responsible for 24% of all male deaths and 7% of all female deaths: these figures rise to over 40% in men in some countries of central and eastern Europe and to 17% in women in the United States. The average loss of life of smokers is 8 years. Among United Kingdom doctors followed for 40 years, overall death rates in middle age were about three times higher among doctors who smoked cigarettes as among doctors who had never smoked regularly. About half of all regular cigarette smokers will eventually be killed by their habit. The important information is that it is never too late to stop smoking: among United Kingdom doctors who stopped smoking, even in middle age, there was a substantial improvement in life expectancy. World-wide, smoking is killing three million people each year and this figure is increasing. In most countries the worst is yet to come, since by the time the young smokers of today reach middle or old age there will be about 10 million deaths/year from tobacco. Approximately 500 million individuals alive today can expect to be killed by tobacco, 250 million of these deaths will occur in middle age. Tobacco is already the biggest cause of adult death in developed countries. Over the next few decades tobacco could well become the biggest cause of adult death in the world. For men in developed countries, the full effects of smoking can already be seen. Tobacco now causes one-third of all male deaths in middle age (plus one fifth in old age). Tobacco is a cause of about half of all male cancer deaths in middle age (plus one-third in old age). Of those who start smoking in their teenage years and keep on smoking, about half will be killed by tobacco. Half of these deaths will be in middle age (35-69) and each will lose an average of 20-25 years of non-smoker life expectancy. In non-smokers in many countries, cancer mortality is decreasing slowly and total mortality rapidly. The war against cancer is being won slowly: the effects of cigarette smoking are holding back this victory. Lung cancer now kills more women in the United States each year than breast cancer. For women in developed countries, the peak of the tobacco epidemic has not yet arrived. Tobacco now causes almost one-third of all deaths in women in middle age in the United States. Although it has only 5% of the world's female population, the United States has 50% of the world's deaths from smoking in women. Tobacco smoking is a major cause of premature death. Throughout Europe, in 1990 tobacco smoking caused three quarters of a million deaths in middle age (between 35 and 69). In the Member States of the European Union in 1990 there were over one quarter of a million deaths in middle age directly caused by tobacco smoking: there were 219700 in men and 31900 in women. There were many more deaths caused by tobacco at older ages. In countries of central and eastern Europe, including the former USSR, there were 441200 deaths in middle age in men and 42100 deaths in women. There is a need for urgent action to help contain this important and unnecessary loss of life. In formulating Recommendations, the European Cancer Experts Consensus Committee recognised that Tobacco Control depends on various parts of society and not only on the individual.
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PMID:Cancer, cigarette smoking and premature death in Europe: a review including the Recommendations of European Cancer Experts Consensus Meeting, Helsinki, October 1996. 919 26

Tamoxifen treatment is a proven therapy for breast cancer that produces a survival advantage when used as an adjuvant, and reduces the incidence of recurrences and controlateral tumor evolution. Although this therapy has a very low toxicity profile, an increase in secondary cancers has been reported. Tamoxifen is suggested to be carcinogenic both through direct genotoxic and epigenetic mechanisms. It is activated by cytochrome P450 to form reactive metabolites that bind covalently to DNA to create adducts. We report two cases that developed acute myeloid leukaemia (AML) during tamoxifen therapy for breast cancer.
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PMID:Acute leukaemia during tamoxifen therapy. 923 14

De novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) is an uncommon form of leukemia characterized by a dyshematopoietic picture accompanying the acute leukemia, a poor response to induction chemotherapy, and a tendency to relapse with pure myelodysplastic syndrome. Cytogenetic information on this entity is scarce, although some cases have been reported to be associated with t(7;11)(p15;p15). A 41-year-old woman who had a history of radiotherapy for breast cancer presented with AML/TMDS and was found to have a unique t(11;12)(p15;q13) abnormality.
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PMID:De novo AML with trilineage myelodysplasia and a novel t(11;12)(p15;q13). 940 80

This laboratory has previously identified a novel TGF-beta inducible early gene (TIEG) in human osteoblasts [Subramaniam et al. (1995): Nucleic Acids Res 23:4907-4912]. Using TIEG specific polyclonal antibody and immunoprecipitation methods in normal human fetal osteoblast cells (hFOB cells), we have now demonstrated that TIEG encodes a 72-kDa protein whose levels are transiently increased at as early as 2 h of TGF-beta treatment. Polarized confocal microscopic analysis of hFOB cells shows a nuclear localized TIEG protein in untreated cells under the conditions described under Methods. Interestingly, the levels of TIEG protein in the nuclei increase when the cells are treated with TGF-beta 1 for 2 h. In contrast, similar analyses of untreated human keratinocytes show a cytoplasmic localized TIEG protein that appears to be translocated to the nucleus after H2O2 treatment. Additional immunohistochemical studies have demonstrated that TIEG protein is expressed in epithelial cells of the placenta, breast, and pancreas, as well as in osteoblast cells of bone and selected other cells of the bone marrow and cerebellum with some cells showing a cytoplasmic localization and others a nuclear localization. All cells of the kidney display negative staining for this protein. Interestingly, a stage specific expression of TIEG protein is found in a dozen breast cancer biopsies, using immunohistochemistry. The cells in normal breast epithelium displays a high expression of TIEG protein, those in the in situ carcinoma display less than one-half of the levels, and those in the invasive carcinoma show a complete absence of the TIEG protein. TIEG has been localized to chromosome 8q22.2 locus, the same locus as the genes involved in osteopetrosis and acute myeloid leukemia and close to the c-myc gene locus and a locus of high polymorphism in cancer biopsies. The correlation between the levels of TIEG protein and the stage of breast cancer, its prime location in human chromosome 8q22.2, and past studies with pancreatic carcinoma, suggests that TIEG may play a role in tumor suppressor gene activities, apoptosis, or some other regulatory function of cell cycle regulation.
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PMID:Tissue, cell type, and breast cancer stage-specific expression of a TGF-beta inducible early transcription factor gene. 944 78

Second malignancy after childhood neoplasms is a well-known complication. However, frequency differs considerably according to the types of primary neoplasm and the specifics of therapy. Ten patients with a second malignancy after being cured of the primary tumor are described. There were 2 patients with acute lymphoblastic leukemia, one with non-Hodgkin's lymphoma, and one with breast cancer after Hodgkin's disease. Two patients with heritable retinoblastoma developed osteosarcomas in the irradiation field after a latent period of 7 and 14 years respectively. There was another osteosarcoma in a Wilms' tumor survivor. One patient with acute lymphoblastic leukemia developed a secondary AML 10 years after achieving initial remission, and a meningioma was diagnosed in another patient with cured acute lymphoblastic leukemia. One patient died of peritoneal sarcomatosis of unknown origin 20 years after the diagnosis of acute myeloid leukemia. All patients received radiotherapy for the primary neoplasms. Secondary neoplasms in other patients were probably missed because they occurred in adulthood when the patients were transferred to other medical centres. It is impossible to trace these patients because central registration of patients with neoplasms is lacking. It is therefore important to establish a central cancer registry for the whole of Switzerland. Second malignancy after childhood cancer is not a rare event and requires long-term follow-up of patients with neoplasms.
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PMID:[Insufficient understanding of second tumors after childhood neoplasms in Switzerland]. 958 99


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