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)

The aim of the present study was to determine whether angelicin is able to increase the expression of gamma-globin genes in human erythroid cells. Angelicin is structurally related to psoralens, a well-known chemical class of photosensitizers used for their antiproliferative activity in treatment of different skin diseases (i.e., psoriasis and vitiligo). To verify the activity of angelicin, we employed two experimental cell systems, the human leukemic K562 cell line and the two-phase liquid culture of human erythroid progenitors isolated from normal donors. The results of our investigation suggest that angelicin, compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and gamma-globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of gamma-globin mRNA accumulation and fetal hemoglobin (HbF) production, even higher than those obtained using hydroxyurea, were detected. These results could have practical relevance, as pharmacologically-mediated regulation of the expression of human gamma-globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including beta-thalassemia and sickle cell anemia.
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PMID:Accumulation of gamma-globin mRNA in human erythroid cells treated with angelicin. 1293 Mar 20

Malignancy in patients with sickle cell disease (SCD) has been previously reported, but the types of cancer and its incidence remain undefined. With the advent of hydroxyurea therapy, there is concern about increasing the cancer risk for patients with SCD. The International Association of Sickle Cell Nurses and Physician Assistants identified 52 cases of cancer (49 patients) among 16,613 patients with SCD followed at 52 institutions. The median age at malignancy diagnosis was 34 years (range, 14 months-62 years). Twenty-one cases (40%) occurred in pediatric patients, primarily leukemia (n = 7) or Wilms' tumor (n = 5), with 15 children surviving. Most adults had solid tumors, especially carcinomas, and only nine were known to be alive. Three patients received hydroxyurea before the diagnosis of malignancy. These data provide essential baseline information for the accurate interpretation of future reports of malignancy in patients with SCD, especially those receiving hydroxyurea therapy.
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PMID:Malignancy in patients with sickle cell disease. 1463 5

The past 3 years have been characterized by a number of impressive advances as well as setbacks in gene therapy for genetic disease. Children with X-linked severe combined immunodeficiency disorder (SCID-X1) have shown almost complete reconstitution of their immune system after receiving retrovirally transduced autologous CD34+ hematopoietic stem cells (HSCs). However, two of 11 treated patients subsequently developed a leukemia-like disease probablydue to the undesired activation of an oncogene. Gene transfer to HSCs resulted in substantial correction of immune function and multi-lineage engraftment in two patients with adenosine deaminase (ADA)-SCID. Several Phase I clinical trials for treatment of hemophilia A and B have been initiated or completed. Partial correction of hemophilia A, albeit transient, has been reported by ex vivo gene transfer to autologous fibroblasts. Intramuscular injection of adeno-associated viral (AAV) vector to patients with severe hemophilia B resulted in evidence of Factor IX gene transfer to skeletal muscle and a separate trial based on hepatic infusion of AAV vector is ongoing. Sustained therapeutic levels of coagulation factor expression have been achieved in preclinical models using retroviral, lentiviral, AAV and high capacity adenoviral vectors. Efficient lentiviral gene transfer to HSC in murine models of beta-thalassemia and sickle cell disease demonstrated sustained phenotypic correction.
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PMID:Update on gene therapy for hereditary hematological disorders. 1503 Feb 82

The present study aimed to determine whether rapamycin could increase the expression of gamma-globin genes in human erythroid cells. Rapamycin is a macrocyclic lactone that possesses immunosuppressive, antifungal and anti-tumour properties. This molecule is approved as an immunosuppressive agent for preventing rejection in patients receiving organ transplantation. To verify the activity of rapamycin, we employed two experimental cell systems, the human leukaemia K562 cell line and the two-phase liquid culture of human erythroid progenitors isolated from normal donors and patients with beta-thalassaemia. The results suggested that rapamycin, when compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and gamma-globin mRNA accumulation in human leukaemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of rapamycin, gamma-globin mRNA accumulation and fetal haemoglobin (HbF) production increased to levels that were higher than those obtained using hydroxyurea. These effects were not associated with inhibition of cell growth. Furthermore, rapamycin was found to increase HbF content in erythroid precursor cells from four beta-thalassaemia patients. These results could have practical relevance, because pharmacologically mediated regulation of the expression of human gamma-globin genes, leading to increased HbF, is considered a potential therapeutic approach in haematological disorders, including beta-thalassaemia and sickle cell anaemia.
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PMID:Rapamycin-mediated induction of gamma-globin mRNA accumulation in human erythroid cells. 1528 57

The authors report the epidemiologic and cytological aspects of 77 patients hospitalized between January 1995 and December 2002 in the clinical hematologic service in University hospital complex of Brazzaville, greatest hospital of the country. During this period, 7155 patients were hospitalized in this service as a frequency of (107%). reported to the number of inpatients admitted on a total of 52,458 patients. The hospital frequency of disease is 0.15%. There's no specific age for this affection (age median = 21-24 years) and all socio-professional categories can be affected with a prevalence of low income patients what complicates extremely the treatment Ratio Man/Woman is 0.8 showing a light female prevalence. On the level of the epidemiologic investigation (limited because of the insufficiency of the means), nothing is retained except rare acute leukaemias secondary to chronic myeloproliferative disorders as well as association with 2 cases of homozygous sickle cell anaemia. Mortality by acute leukaemia in the service is very high, due to lack of equipment. In the cytological plan, there's a light prevalence of the cases of acute lymphoblastic leukaemias of which some could profit from an immunological typing compared to the cases of myeloblastic acute leukaemias
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PMID:[Epidemiologic and cytologic configuration of acute leukaemia at University Hospital of Brazzaville]. 1582 71

Decitabine, a potent DNA methyltransferase inhibitor, which was originally under development by Pharmachemie, is being developed by SuperGen. Pharmachemie had been studying decitabine in phase II clinical trials for several leukemia indications in Europe and the US. Preliminary results indicated that the compound was active in the treatment of myelodysplasia, relapsed leukemia, acute myeloid leukemia and postallogeneic progenitor cell transplant relapse. The compound is in phase II clinical trials with phase III trials scheduled to begin shortly. Decitabine has been used to treat myelodysplastic syndrome in a total of 125 patients, with an overall response rate of 49%. In a study using decitabine to treat chronic myelogenous leukemia in 81 patients, a response rate of 62% among patients in chronic phase of the disease was achieved. In a phase I/II trial designed to establish safety and efficacy in the treatment of sickle cell anemias treatment with decitabine generated a response in 100% of the patients tested: a total of eight patients were enrolled, each experienced elevated levels of fetal hemoglobin. Side effects were minimal and the drug was well tolerated. Plans for additional clinical studies of decitabine as a treatment for sickle cell anemia are underway. A phase II trial using a low dose of decitabine in patients with myelodysplastic syndrome has been completed. Of 66 patients entered, 62 were evaluable. The response rate was 48%, with a median response duration of 40 weeks. The mean survival from the start of therapy was 13 months. In a study with 37 CML patients, a 25% overall response rate was seen in those patients in the blastic phase of the disease, and a 52% response rate was observed in the accelerated phase patients. The most significant side effect was prolonged myelosuppression. The drug suppresses cellular growth in seven human tumor cell lines, possibly by reactivation of certain growth suppressor genes.
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PMID:Decitabine (SuperGen). 1603 61

Autologous hematopoietic cells have been used as targets of gene transfer, with applications in inherited disorders, cell therapy, and acquired immunodeficiency. The types of cells include hematopoietic progenitor cells, lymphocytes, and mesenchymal stem cells. The inherited disorders thus far approached in clinical trials include severe combined immunodeficiency, common variable gamma-chain immunodeficiency, chronic granulomatous disease, and Gaucher disease. Preclinical studies are vigorously under way in thalassemia, sickle cell anemia, Wiskott-Aldrich syndrome and Fanconi anemia. Clinical trials of immunological therapy with gene-modified lymphocytes are under study in the treatment of malignancies. Clinical trials using anti-viral strategies for HIV infection in combination with autologous transplantation have begun, with additional approaches being developed. Gene therapy vectors are being developed to eliminate tumor cells contaminating autologous stem cell products. However, the risk of insertional mutagenesis and the potential for development of leukemia was highlighted by the first gene therapy trials in inherited immunodeficiency syndromes that achieved a therapeutic effect. Despite the slow progress of the field to date, there is extraordinary promise for gene therapy in the future.
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PMID:The current status of gene therapy in autologous transplantation. 1626 58

Successful treatment of many childhood diseases once considered terminal has resulted in the emergence of long-term effects of the disease or consequences of treatment that were previously unrecognized. Many of these long-term effects involve the central nervous system (CNS) and are developmental in the way that they emerge over time. Because we are now able to observe the natural history of childhood diseases such as sickle cell anemia or HIV, or the consequences of treatment of disease such as leukemia, brain tumors, or kidney disease, we are also able to study a number of biological mechanisms that result in long-term neurocognitive impairment. While some of the neurodevelopmental outcomes can be directly linked to structural damage of the CNS, other systems (e.g., hematologic, immunologic, pulmonary) appear to play crucial indirect roles in the development of the CNS and neurocognitive abilities because of the way that they affect the course of brain development and activity of the brain across time. Important interactions between acute disease factors, biological mechanisms, age at the time of disease or treatment effect, and disruptions in patterns of development after successful treatment or management all provide support for a neurodevelopmental model of childhood chronic illness. Testing this model may make it possible to more accurately predict the timing and degree of severity of long-term neurodevelopmental consequences, provide guidance for improved treatment and prevention, and offer better understanding of neurodevelopmental disruptions that occur in other non-chronic illness related disabilities.
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PMID:Neurodevelopment and chronic illness: Mechanisms of disease and treatment. 1706 Dec 86

The significance of warm-reactive autoantibodies in pediatric patients has not been a subject of thorough evaluation. This study was undertaken to correlate the clinical and serologic features of these antibodies to identify predictors of clinical significance. Forty-two consecutive patients with serologically detectable warm-reactive autoantibodies were studied. These patients (21 male, 21 female) had a mean age of 9 years (range: 2 mo to 21 y). Primary diagnoses included autoimmune disorders (14), sickle cell disease (14), viral infection (4), idiopathic autoimmune hemolytic anemia (2), leukemia (2), and other diseases (6). Autoimmune hemolysis, as determined by clinical and laboratory findings, was documented in 24 patients (57%). Serologic studies revealed that all patients demonstrated IgG on their red cells [Direct Antiglobulin Test (DAT) reactivity range: microscopic to 3+]; 17 (40%) also demonstrated complement (DAT reactivity range: microscopic to 2+). There was a correlation between the strength of the DAT for IgG and the presence of complement on the red cells, with both being important predictors of hemolysis. These findings may be useful in predicting the clinical significance of warm-reactive autoantibodies in pediatric patients and allow for more efficient and effective follow-up care.
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PMID:Warm-reactive autoantibodies in pediatric patients: clinical and serologic correlations. 1798 1

Adult F cell numbers are raised in inherited haemoglobin disorders, such as beta-thalassaemia and sickle cell anaemia, hereditary persistence of foetal haemoglobin, and some acquired conditions, such as juvenile myelomonocytic leukaemia, during acute erythropoietic stress and pregnancy. True foetal erythrocytes containing foetal amounts of HbF can also occur in the adult circulation during the leakage of HbF-containing cells from the foetus to the maternal circulation. In normal adults, HbF is restricted to a small proportion (3-7%) of red blood cells (RBC), termed 'F cells'. Techniques estimating the amount of HbF use lysates prepared from RBC, whereas those that estimate the adult F cell count use intact RBC. An accurate assessment of adult F cells in sickle cell disorders is important because increased adult F cells are associated with decreased morbidity in these disorders. In the present study, HbF levels were measured and adult F cell numbers were estimated in 100 blood samples (25 normal individuals, 25 sickle heterozygotes, 25 sickle homozygotes and 25 sickle beta-thalassaemia cases), using high pressure liquid chromatography for HbF levels, and flow cytometry and the Kleihauer-Betke (KB) acid elution microscope slide method for cell counts. Flow cytometry gave a more accurate assessment of adult F cells, eliminating any manual error, as compared to KB, which was less sensitive and precise as it is based on subjective visual interpretation.
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PMID:Evaluation of F cells in sickle cell disorders by flow cytometry -- comparison with the Kleihauer-Betke's slide method. 1798 94


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