The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

Snyder, Robert

doi:10.1111/nyas.12333

Cited by 11 publications

(8 citation statements)

References 41 publications

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“…The use of meta-analysis data as part of a chemical risk assessment has been demonstrated here and provides results not dissimilar to individual studies and previously published estimates. However, the mechanisms of benzene-induced leukemia are still a current topic, (6) with ongoing research in the field likely to provide further insights that could be applied to enhance future risk assessments.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to being widely used in industry, benzene is also found in petrol, exhaust fumes, and tobacco smoke, resulting in the potential for human exposure, not just in occupational settings but also to the wider population. Although the risk of leukemia from occupational exposures to benzene has been well established, the risk to the population from lower environmental levels, such as those from exposure to tobacco smoke, is still not fully understood …”

Section: Introductionmentioning

confidence: 99%

“…Although the risk of leukemia from occupational exposures to benzene has been well established, the risk to the population from lower environmental levels, such as those from exposure to tobacco smoke, is still not fully understood. (6) Tobacco smoke is one of the main potential sources of inhaled benzene exposure for the general population. Several studies have investigated the link between smoking and increased risk of AML, and while these results are not always consistent, there is evidence of a positive association, (7) and both the International Agency for Research on Cancer and the U.S.…”

Section: Introductionmentioning

confidence: 99%

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Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Fiebelkorn

Meredith

2017

Risk Analysis

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Several epidemiological studies have demonstrated an association between occupational benzene exposure and increased leukemia risk, in particular acute myeloid leukemia (AML). However, there is still uncertainty as to the risk to the general population from exposure to lower environmental levels of benzene. To estimate the excess risk of leukemia from low‐dose benzene exposure, various methods for incorporating epidemiological data in quantitative risk assessment were utilized. Tobacco smoke was identified as one of the main potential sources of benzene exposure and was the focus of this exposure assessment, allowing further investigation of the role of benzene in smoking‐induced leukemia. Potency estimates for benzene were generated from individual occupational studies and meta‐analysis data, and an exposure assessment for two smoking subgroups (light and heavy smokers) carried out. Subsequently, various techniques, including life‐table analysis, were then used to evaluate both the excess lifetime risk and the contribution of benzene to smoking‐induced leukemia and AML. The excess lifetime risk for smokers was estimated at between two and six additional leukemia deaths in 10,000 and one to three additional AML deaths in 10,000. The contribution of benzene to smoking‐induced leukemia was estimated at between 9% and 24% (UpperCL 14–31%). For AML this contribution was estimated as 11–30% (UpperCL 22–60%). From the assessments carried out here, it appears there is an increased risk of leukemia from low‐level exposure to benzene and that benzene may contribute up to a third of smoking‐induced leukemia. Comparable results from using methods with varying degrees of complexity were generated.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Fiebelkorn

Meredith

2017

Risk Analysis

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“…U takich osób niedokrwistość aplastyczna może pojawić się nawet już po względnie małych dawkach terapeutycznych leku. Jednak ten typ niedokrwistości może się rozwinąć u każdego chorego leczonego potencjalnie szkodliwym lekiem w dostatecznie dużej dawce przez odpowiednio długi okres [4,23,31,32].…”

Section: Niedokrwistości Indukowane Lekamiunclassified

Drug-induced anemia as an important aspect in patient care

Terpińska¹,

Płaczkowska²,

Jurkowska³

et al. 2018

Farm Pol.

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Drug-induced anemia as an important aspect in patient care • Anemia is a pathological condition caused by an imbalance between the body's oxygen demand and its limited supply because of disturbances in the number, structure and function of red blood cells. This condition manifests with many clinical symptoms that, although they are not specific, are common to various types of anemia, regardless of inducing factors. Therefore, early and proper diagnosis of anemia, as well as implementing appropriate therapeutic actions are difficult. Decreased hemoglobin concentration and/or red blood cell counts are the basic laboratory parameters for diagnosing and assessing the severity of anemia and these parameters should be interpreted along with other laboratory tests. The proper diagnosis of anemia and determination of its cause is the basis for effective treatment. Haematological abnormalities are one of the possible side effects when using pharmacotherapy and among them drug-induced anemias are an important group. Negative or toxic effects of the drug may favor the development of aplastic, immune haemolytic, haemolytic, megaloblastic and sideroblastic anemias. Cytostatics, immunosuppressive and non-steroidal anti-inflammatory drugs play an important role in the induction of hematological disorders. The possibility of anemia occurrence is also important when using routine pharmacotherapy or OTC drugs. Knowledge of the mechanisms, causes of abnormalities and currently recommended laboratory markers in the diagnosis of anemia is helpful in effective medical and pharmaceutical care of the patient.

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“…Hematopoietic stem cells (HSCs) exist in hematopoietic niches. The hypoxic microenvironment helps to maintain their energetic metabolism mainly based on anaerobic glycolysis, which is necessary to keep their stemness and quiescence [ 12 , 13 ]. It is now well established that HIF-1α is highly expressed in long term proliferating HSCs [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Global Identification of HIF-1α Target Genes in Benzene Poisoning Mouse Bone Marrow Cells

Man

Meng

Sun

et al. 2018

IJERPH

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Benzene is a hematopoietic toxicant, and hematopoietic cells in bone marrow (BM) are one of the main targets for its action, especially hematopoietic stem cells (HSCs). Hypoxia-inducible factor-1α (HIF-1α) is associated with the metabolism and physiological functions of HSCs. We previously found that the mechanism of regulation of HIF-1α is involved in benzene-induced hematopoietic toxicity. In this study, chromatin immunoprecipitation sequencing (ChIP-Seq) technologies were used to analyze the genome-wide binding spectrum of HIF-1α in mouse BM cells, and specific HIF-1α target genes and pathways associated with benzene toxicity were screened and validated. By application of the ChIP-Seq technique, we identified target genes HIF-1α directly binds to and regulates. Forty-two differentially down-regulated genes containing the HIF-1α specific binding site hypoxia response element (HRE) were found, of which 25 genes were with biological function. Moreover, the enrichment analysis of signal pathways indicated that these genes were significantly enriched in the Jak-STAT signaling pathway, Natural killer cell mediated cytotoxicity, the Fc epsilon RI signaling pathway, Pyrimidine metabolism, the T cell receptor signaling pathway, and Transcriptional misregulation in cancer. After verification, 11 genes involved in HSC self-renewal, cell cycle, differentiation, and apoptosis pathways were found to be significantly reduced, and may participate in benzene-induced hematotoxicity. Our study provides a new academic clue for the mechanism of benzene hematotoxicity.

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The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

Cited by 11 publications

References 41 publications

Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Estimation of the Leukemia Risk in Human Populations Exposed to Benzene from Tobacco Smoke Using Epidemiological Data

Drug-induced anemia as an important aspect in patient care

Global Identification of HIF-1α Target Genes in Benzene Poisoning Mouse Bone Marrow Cells

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