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 embryonal stage in mammalians is characterized by a quick proliferation and differentiation of cells. The special features of this stage of development in all living beings is therefore an increased sensitivity for the exposure with ionizing radiation. Radiation exposure during the prenatal development can therefore lead to various impairments, which can be short-termed or long-termed, showing effects even in the postnatal period. The pattern of radiation induced effects is dependent upon the radiation dose on the one hand and upon the stage of fetal development when radiation exposure occurs on the other hand. Radiation induced effects can be growth retardation, malformations, functional impairments or death as well as increased occurrence of cancer and leukemia during childhood. The main effects of a radiation exposure in the fetal period are: 1) lethal effects for the embryo, 2) malformations and changes in growth or other functional changes, 3) mental retardation, 4) induction of malignomas including leukemia. Lethal effects can be induced experimentally in animals by relatively low radiation doses of 10 cGy, administered before or immediately after the implantation of the embryo. Malformations can be induced if the exposure occurs during the period of organogenesis especially if the radiation exposure occurs during the active stage of increased cell formation and cell differentiation of a specific organ. For many types of effects of ionizing radiation especially for the death of the embryo or fetus and for macroscopic anatomical malformation a dose-effect relationship with certain threshold doses can be supposed. This threshold dose is not smaller than 5 cGy if the exposure results from a low level radiation with low LET> Radiation exposure at the end of the organogenesis and during the following fetal period can induce growth retardation and functional disturbances, which are characterized by abnormalities in the postnatal period. Of special importance are the abnormalities of the CNS, like mental retardation particularly if the radiation exposure occurred during the interval between the 8th and 15th week of pregnancy. During that time period cell formation for the development of the frontal brain occurs. The induction of this type of abnormalities as well as of other malformations is due to non stochastic effects. A threshold dose of 5 cGy ist discussed. The induction of malignancies and leukemia as a consequence of a radiation exposure in the prenatal period is to be seen as a deterministic (non stochastic) radiation effect. The sensitivity of the fetus for these effects ist 2 to 3 times higher than that of adults.
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PMID:[Exposure to radioactive iodine in pregnancy: significance for mother and child]. 944 52

A recently described atypical myeloproliferative disorder is invariably associated with reciprocal translocations involving 8p11-12. The most common rearrangement is a t(8;13)(p11;q11-12). Here we determine that this translocation results in the fusion of the fibroblast growth factor receptor 1 gene (FGFR1), a member of the receptor tyrosine kinase family at 8p11, to a novel gene at 13q11-12 designated RAMP . The predicted RAMP protein exhibits strong homology to the product of a recently cloned candidate gene for X-linked mental retardation, DXS6673E . We also provide the first report of a novel, putative metal-binding motif, present as five tandem repeats in both RAMP and DXS6673E. RT-PCR detected only one of the two possible fusion transcripts, encoding a product in which the N-terminal 641 amino acids of RAMP become joined to the tyrosine kinase domain of FGFR1. Receptor tyrosine kinases are not commonly involved in the formation of tumour-specific fusion proteins. However, the previous reports of involvement of receptor tyrosine kinases in fusion proteins in non-Hodgkin's lymphoma, chronic myelomonocytic leukaemia and papillary thyroid carcinoma described similar rearrangements. By analogy with these, we propose that the RAMP-FGFR1 fusion product will contribute to progression of this myeloproliferative disorder by constitutive activation of tyrosine kinase function.
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PMID:The t(8;13)(p11;q11-12) rearrangement associated with an atypical myeloproliferative disorder fuses the fibroblast growth factor receptor 1 gene to a novel gene RAMP. 949 16

CBP and its homolog p300 are large nuclear molecules that coordinate a variety of transcriptional pathways with chromatin remodeling. They interact with transcriptional activators as well as repressors, direct chromatin-mediated transcription, function in TP53-mediated apoptosis, and participate in terminal differentiation of certain tissue types. Recent evidence suggests that the demand for CBP/p300 is greater than the supply, and that competition for CBP/p300 might play an important role in cell growth regulation. Alterations of the human CBP gene have been implicated in hematological malignancies as well as in congenital malformation and mental retardation. Likewise, the p300 gene has been recently implicated in leukemia and mutations in both alleles have been observed in gastric and colorectal carcinomas. The role of these proteins in human disease coupled with biochemical evidence suggests that CBP and p300 are tumor suppressor proteins essential in cell-cycle control, cellular differentiation and human development.
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PMID:Conjunction dysfunction: CBP/p300 in human disease. 961 1

Cosmic radiation is an occupational hazard to commercial and military flight crews. Aside from the direct risk to aviators, this ionizing radiation is a hazard to the fetuses of pregnant crewmembers and passengers. Animal studies of low dose ionizing radiation exposures, and human studies following high (lose exposures, suggest that pregnant avia tors may inadvertently subject their fetuses to a risk of decreased cognitive capacity or frank mental retardation, as well as childhood leukemia. Flight attendants sometimes unknowingly exceed recommended maximum cosmic radiation doses to their fetuses, raising social, ethical, and legal issues.
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PMID:Pregnancy and in-flight cosmic radiation. 1033 54

The 1986 nuclear reactor accident at Chernobyl caused nonuniform radiocontamination of air and land, primarily within regions of the former Soviet Union and Western Europe. Major exposure groups included the reactor workers, villagers evacuated from within 30 km of the accident, the "liquidators" who decontaminated the evacuation zone afterward, those in radiocontaminated villages not evacuated, and "others" not in the latter categories. The possibility of being exposed to radiation caused considerable anxiety, especially among pregnant women. Were teratogenic levels of radiation (> or = 0.1 Gy) exposure attained? To date there is no consistent proof that this level of radiation exposure was received. Nevertheless, thousands of induced abortions were performed. Radioiodine (I-131) caused thyroid cancer in young children in portions of Belarus, the Ukraine, and Russia. It is not known but very possible that I-131 fetal thyroid exposure contributed to this observation. The relationship between mental retardation and radiation exposure has not been confirmed. Leukemia and other cancers, while predicted for the liquidators (mainly males), has not been found in the other exposure groups at this time. Investigations of aborted fetuses and newborns in Belarus showed an increase in the frequency of both congenital and fetal abnormalities in high and low Cs-137 contaminated regions. This study is unreliable due to detection and selection biases. Accident and environmental factors unrelated to radiation doses may have contributed to these observations. Occasional positive teratogenic studies in less contaminated regions of Western Europe are suspect because of the low radiation doses received. There is no substantive proof regarding radiation-induced teratogenic effects from the Chernobyl accident.
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PMID:Teratogen update: radiation and Chernobyl. 1044 Jul 82

The constitutional chromosomal deletion within the short arm of one copy of chromosome 11, at band p13, which often correlated with WAGR syndrome consisting of Wilms' tumor with aniridia, genitourinary malformation, and mental retardation, provided the first clue to the genetic events in the development of Wilms' tumor. WT1 gene is encoded by 10 exons, resulting in messenger RNA subject to a complex pattern of alternative splicing. WT1 gene encodes a zinc finger transcription factor, which binds to GC-rich sequences and functions as a transcriptional activator or repressor for many growth factor genes. WT 1 protein is mainly expressed in developing kidney, testis, and ovary, indicating that it is involved in the differentiation of genitourinary tissues, all thought to be the sites of origin of Wilms' tumor. The point mutation of WT1 results in Denys-Drash syndrome. The other Wilms' tumor gene, WT2 at 11p15.5, is linked to Beckwith-Wiedemann syndrome. The possibility that WT1 is involved in the etiology of rhabdoid tumor of the kidney was discussed. WT1 is expressed in immortalized hematologic cells such as EBV-LCL and hematologic malignancies, but not in PBL or IL-2L. High level WT1 expression in leukemia cells and a poor prognosis are linked in patients with leukemia, making the gene a novel marker for leukemia cells. A correlated expression between WT1 and mdr-1 in vincristine resistant cells indicates a close relation with multi-drug resistance and is a promising diagnostic marker for chemoresistance in hematologic malignancies.
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PMID:The role of Wilms' tumor genes. 1068 7

The EZH2 gene is a homolog of the Drosophila Polycomb group (PcG) gene enhancer of zest, a crucial regulator of homeotic gene expression. Several lines of evidence suggest a critical role for the EZH2 protein during normal and perturbed development of the haematopoietic and central nervous systems. Indeed, the EZH2 protein has been shown to associate with the Vav proto-oncoprotein and with the XNP protein, the product of a mental retardation gene. The EZH2 gene was previously reported to be located on chromosome 21q22 and was proposed as a candidate gene for some characteristics of the Down syndrome phenotype. We report here the genomic structure and fine mapping of the EZH2 gene. We demonstrate that the functional gene actually maps to chromosome 7q35 and that the sequence previously isolated from a chromosome 21 cosmid corresponds to a pseudogene. Finally, the nature of the EZH2 protein and its mapping to the critical region for malignant myeloid disorders lead us to propose the EZH2 gene is involved in the pathogenesis of 7q35-q36 aberrations in myeloid leukaemia.
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PMID:The human EZH2 gene: genomic organisation and revised mapping in 7q35 within the critical region for malignant myeloid disorders. 1078 Jul 82

Larvae homozygous for the recessive lethal allele without children(rgl) (woc(rgl)) fail to pupariate. Application of exogenous 20-hydroxyecdysone elicits puparium formation and pupation. Ecdysteroid titer measurements on mutant larvae show an endocrine deficiency in the brain-ring gland complex, which normally synthesizes ecdysone, resulting in a failure of the larvae to achieve a threshold whole body hormone titer necessary for molting. Ultrastructural investigation revealed extensive degeneration of the prothoracic cells of the ring gland in older larvae. The woc gene, located in polytene chromosomal region 97F, consists of 11 exons. A 6.8-kb transcript is expressed throughout development but is absent in the mutant woc(rgl) larvae. The woc gene encodes a protein of 187 kDa. Eight zinc fingers of the C2-C2 type point to a possible function as a transcription factor. The woc protein shows considerable homology to human proteins which have been implicated in both mental retardation and a leukemia/lymphoma syndrome.
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PMID:The mutation without children(rgl) causes ecdysteroid deficiency in third-instar larvae of Drosophila melanogaster. 1099 70

Down syndrome, as a phenotypic result of trisomy 21, is a complex condition with a set of over 30 phenotypic features, which manifest themselves with varying frequencies among affected individuals. The importance for molecular medicine of understanding the molecular mechanisms underlying Down syndrome becomes fully appreciated when a striking feature of Down syndrome is taken into account: that the overdose of otherwise perfectly normal genes causes disorders of human health, indistinguishable from major public health problems of the general population, such as mandatory early onset Alzheimer s degeneration, increased risk of leukemia, and protection from cancer of solid tissues. The DNA sequence of human chromosome 21 is, at the moment, the most complete piece of DNA sequence known in the whole of human genome. The challenge for the future is an integrated, multidisciplinary approach to the molecular biology of chromosome 21 genes, in conjunction with the research into the variation in their genotype, expression, and function in the normal population, in Down syndrome individuals with well-characterized phenotypic traits, and in euploid patients suffering from diseases associated with phenotypic components of Down syndrome: mental retardation, developmental defects, hematological and solid tissue malignancies, and Alzheimer s disease.
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PMID:Functional genomics of the Down syndrome. 1147 Nov 93

Male and female germ cells vary in their sensitivity to the mutagenic effects of chemotherapy and radiotherapy, depending on their stage of maturation and the agent used. Although sperm DNA damage exists following treatment, no increase in genetic defects or congenital malformations was detected among children conceived to parents who have previously undergone chemotherapy or radiotherapy. The use of assisted reproductive technologies and micromanipulation techniques might increase this risk; hence caution should be exercised. In female cancer patients, miscarriage and congenital malformations are not increased following chemotherapy. However, when IVF and embryo cryopreservation is practised between or shortly after treatment, possible genetic risks to the growing oocytes exist, and hence the babies should be screened. During pregnancy, the potential teratogenic effects of chemotherapy influence the choice and timing of therapy. Termination is usually recommended in the first trimester. Second- and third-trimester exposure does not usually increase the teratogenic risk and cognitive development, but it may increase the risk of poor obstetric outcome and fetal myelosuppression. During the first two weeks after fertilization of the embryo, radiation is lethal but not teratogenic. High doses of radiation during pregnancy induce anomalies, impaired growth and mental retardation, and there may be an increased risk of childhood leukaemia and other tumours in the offspring.
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PMID:Genetic and teratogenic effects of cancer treatments on gametes and embryos. 1147 52


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