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)

Acute myeloid leukemia and chronic lymphocytic leukemia are associated with benzene exposure. In mice, benzene induces chromosomal breaks as a primary mode of genotoxicity in the bone marrow (BM). Benzene-induced DNA lesions can lead to changes in hematopoietic stem cells (HSC) that give rise to leukemic clones. To gain insight into the mechanism of benzene-induced leukemia, we investigated the DNA damage repair and response pathways in total bone marrow and bone marrow fractions enriched for HSC from male 129/SvJ mice exposed to benzene by inhalation. Mice exposed to 100 ppm benzene for 6h per day, 5 days per week for 2 week showed significant hematotoxicity and genotoxicity compared to air-exposed control mice. Benzene exposure did not alter the level of apoptosis in BM or the percentage of HSC in BM. RNA isolated from total BM cells and the enriched HSC fractions from benzene-exposed and air-exposed mice was used for microarray analysis and quantitative real-time RT-PCR. Interestingly, mRNA levels of DNA repair genes representing distinct repair pathways were largely unaffected by benzene exposure, whereas altered mRNA expression of various apoptosis, cell cycle, and growth control genes was observed in samples from benzene-exposed mice. Differences in gene expression profiles were observed between total BM and HSC. Notably, p21 mRNA was highly induced in BM but was not altered in HSC following benzene exposure. The gene expression pattern suggests that HSC isolated immediately following a 2 weeks exposure to 100 ppm benzene were not actively proliferating. Understanding the toxicogenomic profile of the specific target cell population involved in the development of benzene-associated diseases may lead to a better understanding of the mechanism of benzene-induced leukemia and may identify important interindividual and tissue susceptibility factors.
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PMID:Gene expression profile in bone marrow and hematopoietic stem cells in mice exposed to inhaled benzene. 1512 Sep 71

Benzene has been used in various industries as glues or solvents in Korea. Since 1981, a preparation containing more than 1% benzene is not allowed to be manufactured, used or dealt with in the workplace, except in laboratories and in those situations benzene must be used in a completely sealed process as specified in Industrial Safety and Health Act (ISHA). Claims for compensation of hematopoietic diseases related to benzene have been rising even though the work environment has been improved. This study was conducted to assess the status of benzene exposure in different industries in Korea. We reviewed the claimed cases investigated by the Korea Occupational Safety and Health Agency (KOSHA) between 1992 and 2000. The Survey of National Work Environment Status in 1998 was analyzed to assume the number of workers and factories exposed to benzene. In 2000, six factories were investigated to evaluate benzene exposure. Personal air monitoring was performed in 61 workers and urine samples were collected from 57 workers to measure trans,trans-muconic acid (t,t-MA). Hematologic examination has performed. Thirty-four cases of hematopoietic diseases were investigated by KOSHA including eight cases of myelodysplastic syndrome and eight cases of acute myelocytic leukemia. Eight cases were accepted as related to benzene exposure. The number of workers possibly exposed to benzene can be estimated to be 196,182 workers from 6219 factories based on the database. The geometric mean of benzene in air was 0.094 (0.005-5.311) ppm. Seven samples were higher than 1 ppm but they did not go over the 10 ppm occupational exposure limit (OEL) value in Korea. The geometric mean of trans,trans-muconic acid in urine was 0.966 (0.24-2.74) mg/g creatinine. The benzene exposure level was low except in a factory where benzene was used to polymerize other chemicals. The ambient benzene from 0.1 to 1 ppm was significantly correlated with urine t,t-MA concentration (r=0.733, p<0.01). Hematologic parameters did not show significant difference among groups divided into the level of exposure. Korean workers were not highly exposed to benzene and the level of exposure was mostly less than 1 ppm. However, there might be an excessive risk of hematopoietic disorders due to relatively high past exposure. The OEL value of benzene was amended to 1 ppm from 10 ppm in 2002 and was effective since July 2003.
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PMID:Occupational exposure to benzene in South Korea. 1593 1

Benzene and benzene-containing products and solvents have long been associated with bone marrow toxicity. Both animal studies and human epidemiological studies have shown statistically significant increases of leukemia and other lymphohematopoietic cancers in workers exposed to benzene. The most common leukemia that has been associated with benzene exposure, also called benzene poisoning, is acute myelocytic leukemia (AML). A review of the epidemiological literature on workers exposed to benzene or benzene-containing solvents and products shows, without question, that this exposure is significantly related to other types of leukemia and lymphoma. In this article, we review the literature on the relationship between benzene exposure and chronic myelogenous leukemia (CML) and find that benzene and benzene-containing products are significantly related to morbidity and mortality from CML.
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PMID:Dangerous and cancer-causing properties of products and chemicals in the oil refining and petrochemical industries. Part XXX: Causal relationship between chronic myelogenous leukemia and benzene-containing solvents. 1711 96

Benzene risk assessment indicates that exposure to a time-weighted average (TWA) of 1-5 parts per million (ppm) benzene in ambient air for 40 years is associated with an increased risk of acute myeloid leukemia. Decreased white blood cell count, platelet count and other hematological indices have also been observed in persons exposed to as low as 1 ppm airborne benzene. Evidence from studies worldwide consistently shows elevated levels of benzene biomarkers that are equivalent to 0.1-2 ppm benzene in ambient air, or even higher in the general population without occupational exposure to benzene (including children). The public health significance of these observations depends on to what extent these levels reflect actual benzene exposure, and whether such exposures are life-long or at least occur frequently enough to pose a possible health threat. We reviewed the evidence and discussed possible explanations for these observations. It was concluded that while there is reason to suspect that benzene contributes significantly to elevated levels of biomarkers in the general population, there is growing concern that this cannot be definitively ascertained without concomitant consideration of the role of other factors such as metabolic polymorphisms and sources of biomarkers other than benzene, which have been insufficiently studied to date. Such studies are urgently needed for valid assessment of this potential public health problem.
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PMID:A critique of benzene exposure in the general population. 1726 27

Benzene-induced acute myeloid leukemia (AML) is considered a secondary form of AML, based both in theory and on limited cohort observations. Its latency, cytogenetic aberrations, and clinical features are thought similar to, or identical with, AML resulting from the use of modern day cytotoxic agents for chemotherapy and immunotherapy. Although distinction between secondary AML and the far more common de novo AML is difficult to establish with certainty in any given case, latency from toxic therapeutic and environmental exposure and certain clinical and pathological features generally separate these two entities. AML is the only human neoplasm proven to be potentially caused by benzene, which actually is an obsolete form of chemotherapy. Despite many years of environmental regulation, alleged toxic exposure to this ubiquitous chemical has become an expanding area of litigation. A review of benzene-induced AML suggests that, in developed countries, this entity should no longer merit serious consideration among workers in the modern petrochemical industry and related fields.
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PMID:Benzene-induced acute myeloid leukemia: a clinician's perspective. 1750 65

Benzene exposure has been shown to be related to acute myelogenous leukemia, while the association with multiple myeloma and non-Hodgkin lymphoma has been a much-debated issue. We performed a historical cohort study to investigate whether workers employed in Norway's upstream petroleum industry exposed to crude oil and other products containing benzene have an increased risk of developing various subtypes of hematologic neoplasms. Using the Norwegian Registry of Employers and Employees we included all 27,919 offshore workers registered from 1981 to 2003 and 366,114 referents from the general working population matched by gender, age, and community of residence. The cohort was linked to the Cancer Registry of Norway. Workers in the job category "upstream operator offshore", having the most extensive contact with crude oil, had an excess risk of hematologic neoplasms (blood and bone marrow) (rate ratio (RR) 1.90, 95% confidence interval (95% CI): 1.19-3.02). This was ascribed to an increased risk of acute myelogenous leukemia (RR 2.89, 95% CI: 1.25-6.67) and multiple myeloma (RR 2.49, 95% CI: 1.21-5.13). There were no statistical differences between the groups in respect to non-Hodgkin lymphoma. The results suggest that benzene exposure, which most probably caused the increased risk of acute myelogenous leukemia, also resulted in an increased risk of multiple myeloma.
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PMID:Increased risk of acute myelogenous leukemia and multiple myeloma in a historical cohort of upstream petroleum workers exposed to crude oil. 1790 34

Benzene is a well-known environmental pollutant that can induce hematotoxicity, aplastic anemia, acute myelogenous leukemia, and lymphoma. However, although benzene metabolites are known to induce oxidative stress and disrupt the cell cycle, the mechanism underlying lympho/leukemogenicity is not fully understood. Caspase-4 (alias caspase-11) and -12 are inflammatory caspases implicated in inflammation and endoplasmic reticulum stress-induced apoptosis. The objectives of this study were to investigate the altered expression of caspase-4 and -12 in mouse bone marrow after benzene exposure and to determine whether their alterations are associated with benzene-induced bone marrow toxicity, especially cellular apoptosis. In addition, we evaluated whether the p53 gene is involved in regulating the mechanism, using both wild-type (WT) mice and mice lacking the p53 gene. For this study, 8-week-old C57BL/6 mice [WT and p53 knockout (KO)] were administered a benzene solution (150 mg/kg diluted in corn oil) via oral gavage once daily, 5 days/week, for 1 or 2 weeks. Blood and bone marrow cells were collected and cell counts were measured using a Coulter counter. Total mRNA and protein extracts were prepared from the harvested bone marrow cells. Then qRT-PCR and Western blotting were performed to detect changes in the caspases at the mRNA and protein level, respectively. A DNA fragmentation assay and Annexin-V staining were carried out on the bone marrow cells to detect apoptosis. Results indicated that when compared to the control, leukocyte number and bone marrow cellularity decreased significantly in WT mice. The expression of caspase-4 and -12 mRNA increased significantly after 12 days of benzene treatment in the bone marrow cells of benzene-exposed p53KO mice. However, apoptosis detection assays indicated no evidence of apoptosis in p53KO or WT mice. In addition, no changes of other apoptosis-related caspases, such as caspase-3 and -9, were found in WT or p53KO mice at the level of mRNA and proteins. These results indicated that upregulation of caspase-4 and -12 in mice lacking the p53 gene is not associated with cellular apoptosis. In conclusion, caspase-4 and -12 can be activated by benzene treatment without inducing cell apoptosis in mouse bone marrow, which are partly under the regulation of the p53 gene.
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PMID:Benzene activates caspase-4 and -12 at the transcription level, without an association with apoptosis, in mouse bone marrow cells lacking the p53 gene. 1932 98

Benzene-caused hematologic neoplasms may be recognized as an occupational disease (OD) according to the German ordinance on ODs. At present, the OD No. 1303 covers heterogeneous diseases and various chemical agents triggering these diseases. The members of the medical advisory board specializing in ODs within the Ministry of Employment and Social Affairs recently proposed excluding "diseases of the blood, the hematopoietic and lymphatic system caused by benzene" from OD No. 1303 and classifying them as a separate OD. Benzene is generally acknowledged as a cause of acute myeloid leukemia, proven by numerous epidemiologic studies. However, there is less epidemiologic evidence of its association with other hematologic neoplasms, notably non-Hodgkin's lymphoma (NHL). To clarify this issue, the experts evaluated international literature and concluded that all kinds of myeloid and lymphoid malignancies including their prestages can be caused by occupational benzene exposure. Hence, physicians should ask patients about occupational benzene exposure and report any kind of diagnosed hematologic neoplasms, including their prestages, as suspected OD. The advisory board considered that a dose range starting from 10 ppm-years (cumulative benzene exposure) is sufficient for a > 50% probability of causing leukemias according to the WHO classification, including chronic lymphatic leukemia, and the potential preleukemias aplastic anemia and myelodysplastic syndrome, but excluding chronic myeloid leukemia (CML). For NHL and myeloproliferative diseases (including CML) the present epidemiologic evidence is considered not to be sufficient to describe a precise dose-effect relationship.
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PMID:[Paradigm change in the assessment of myeloid and lymphoid neoplasms associated with occupational benzene exposure]. 1933 9

This research focused on three major questions regarding benzene-induced hematopoietic neoplasms (HPNs). First, why are HPNs induced equivocally and at only threshold level with low-dose benzene exposure despite the significant genotoxicity of benzene even at low doses both in experiments and in epidemiology? Second, why is there no linear increase in incidence at high-dose exposure despite a lower acute toxicity (LD(50) > 1000 mg/kg body weight; WHO, 2003, Benzene in drinking-water. Background document for development of WHO Guidelines for Drinking-Water Quality)? Third, why are particular acute myeloid leukemias (AMLs) not commonly observed in mice, although AMLs are frequently observed in human cases of occupational exposure to benzene? In this study, we hypothesized that the threshold-like equivocal induction of HPNs at low-dose benzene exposure is based on DNA repair potential in wild-type mice and that the limited increase in HPNs at a high-dose exposure is due to excessive apoptosis in wild-type mice. To determine whether Trp53 deficiency satisfies the above hypotheses by eliminating or reducing DNA repair and by allowing cells to escape apoptosis, we evaluated the incidence of benzene-induced HPNs in Trp53-deficient C57BL/6 mice with specific regard to AMLs. We also used C3H/He mice, AML prone, with Trp53 deficiency to explore whether a higher incidence of AMLs on benzene exposure might explain the above human-murine differences. As a result, heterozygous Trp53-deficient mice of both strains showed a nonthreshold response of the incidence of HPNs at the lower dose, whereas both strains showed an increasing HPN incidence up to 100% with increasing benzene exposure dose, including AMLs, that developed 38% of heterozygous Trp53-deficient C3H/He mice compared to only 9% of wild-type mice exposed to the high dose. The detection of AMLs in heterozygous Trp53-deficient mice, even in the C57BL/6 strain, implies that benzene may be a potent inducer of AMLs also in mice with some strain differences.
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PMID:Benzene-induced hematopoietic neoplasms including myeloid leukemia in Trp53-deficient C57BL/6 and C3H/He mice. 1947 38

Benzene exposure is well demonstrated as a cause of acute myelogenous leukemia, but not of chronic myelogenous leukemia. Previous literature reviews based on case series and cohort studies have not shown an association. We have now conducted a literature search for case-control studies that examine the association between benzene exposure and chronic myelogenous leukemia. Six case-control studies have been found. These derive from occupational groups, cancer registries, and a clinical laboratory. Their exposure ascertainments are all based on job histories, job-exposure matricies, or industrial hygiene data. The odds ratios (ORs) for individual studies range from 0.73 to 1.2. The pooled OR is 1.003 with 95% confidence interval (CI) of 0.94-1.07 (p=0.98) for both a fixed effects model and a random effects model. The case-control literature indicates that chronic myelogenous leukemia does not appear to be related to benzene exposure.
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PMID:Chronic myelogenous leukemia and benzene exposure: a systematic review and meta-analysis of the case-control literature. 1969 37


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