Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions

Omori, Fusayuki; Okamura, Seiichi; Shimoda, Kazuya; Otsuka, Takeshi; Harada, Mine; Niho, Yoshiyuki

doi:10.1007/bf02171759

Cited by 43 publications

(22 citation statements)

References 25 publications

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“…Cytokine levels were similar in the two groups. Previous studies have shown that G-CSF, IL-6, erythropoietin, and TNF-ax are elevated in patients with myelodysplastic syndromes (11)(12)(13) (36), which recent studies suggest plays an important role in the development of leukemias and lymphomas (37,38).…”

Section: Discussionmentioning

confidence: 99%

“…Cytokine measurements were prioritized on the basis of alterations previously detected in patients with the myelodysplastic syndrome (11)(12)(13). Plasma levels of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor both tend to be elevated in patients with aplastic anemia (13).…”

Section: Subject Enrollmentmentioning

confidence: 99%

“…Plasma levels of granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor both tend to be elevated in patients with aplastic anemia (13). Therefore, because of the limited volume of plasma available, we chose to measure G-CSF alone.…”

Section: Subject Enrollmentmentioning

confidence: 99%

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An epidemiologic study of early biologic effects of benzene in Chinese workers.

Rothman

Smith

Hayes

et al. 1996

Environ Health Perspect

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Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cell levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cell levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colonystimulating factor, tissue necrosis factor-a) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and No variants, which arise from gene inactivation. The NN (but not NO) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean ± SD, 13.9 ± 8.4 mutants per million cells versus 7.4 ± 5.2 per million cells, respectively; p=0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Subject Enrollmentmentioning

confidence: 99%

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An epidemiologic study of early biologic effects of benzene in Chinese workers.

Rothman

Smith

Hayes

et al. 1996

Environ Health Perspect

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“…Decreased numbers of monosomy 7 cells relative to diploid cells were evident in cultures after 4 days at low GCSF concentrations, but significantly more monosomy 7 cells were seen growing at very high GCSF concentrations, in the range of those present in the circulation of patients with marrow failure (11,14) (Fig. 1C).…”

Section: Gcsf Promotes Expansion Of Preexisting Monosomy 7 Clonesmentioning

confidence: 93%

“…In one study of marrow-failure patients, only 28% of chromosomal abnormalities detected by FISH were observed by conventional cytogenetics (10). GCSF levels are generally an order of magnitude higher in severe AA than in neutropenia of other origins (11,12). An increased prevalence of monosomy 7 among untreated cases could, therefore, be explained by high endogenous levels of GCSF in AA.…”

mentioning

confidence: 99%

Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor

Sloand

Yong²,

Ramkissoon

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

107

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Granulocyte colony-stimulating factor (GCSF) administration has been linked to the development of monosomy 7 in severe congenital neutropenia and aplastic anemia. We assessed the effect of pharmacologic doses of GCSF on monosomy 7 cells to determine whether this chromosomal abnormality developed de novo or arose as a result of favored expansion of a preexisting clone. Fluorescence in situ hybridization (FISH) of chromosome 7 was used to identify small populations of aneuploid cells. When bone marrow mononuclear cells from patients with monosomy 7 were cultured with 400 ng͞ml GCSF, all samples showed significant increases in the proportion of monosomy 7 cells. In contrast, bone marrow from karyotypically normal aplastic anemia, myelodysplastic syndrome, or healthy individuals did not show an increase in monosomy 7 cells in culture. In bone marrow CD34 cells of patients with myelodysplastic syndrome and monosomy 7, GCSF receptor (GCSFR) protein was increased. Although no mutation was found in genomic GCSFR DNA, CD34 cells showed increased expression of the GCSFR class IV mRNA isoform, which is defective in signaling cellular differentiation. GCSFR signal transduction via the Jak͞Stat system was abnormal in monosomy 7 CD34 cells, with increased phosphorylated signal transducer and activation of transcription protein, STAT1-P, and increased STAT5-P relative to STAT3-P. Our results suggest that pharmacologic doses of GCSF increase the proportion of preexisting monosomy 7 cells. The abnormal response of monosomy 7 cells to GCSF would be explained by the expansion of undifferentiated monosomy 7 clones expressing the class IV GCSFR, which is defective in signaling cell maturation.hematopoiesis ͉ myelodysplasia ͉ clonal evolution ͉ leukemia ͉ marrow failure

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Immune status of patients with inherited bone marrow failure syndromes

et al. 2015

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Immune function abnormalities have been reported in patients with Fanconi anemia (FA), dyskeratosis congenita (DC) and, rarely, in Shwachman-Diamond syndrome (SDS) and Diamond-Blackfan anemia (DBA), but large systematic studies are lacking. We assessed immunological parameters in 118 patients with these syndromes and 202 unaffected relatives. We compared results in patients with reference values, and with values in relatives after adjusting for age, sex, corticosteroid-treatment and severe bone marrow failure (BMF). Adult patients (≥18 years) with FA had significantly lower immunoglobulins (IgG, IgA and IgM), total lymphocytes and CD4 T-cells than reference values or adult relatives (p<0.001); children with FA had normal values. Both children and adults with FA had lower B- and NK-cells (p<0.01) than relatives or reference values. Patients with DC had essentially normal immunoglobulins but lower total lymphocytes than reference values or relatives, and lower T-, B- and NK-cells; these changes were more marked in children than adults (p<0.01). Most patients with DBA and SDS had normal immunoglobulins and lymphocytes. Lymphoproliferative responses, serum cytokine levels, including TNF-α and IFN-γ, and cytokine levels in supernatants from phytohemagglutinin-stimulated cultures were similar across patient groups and relatives. Only patients with severe BMF, particularly those with FA and DC, had higher serum G-CSF and Flt3-ligand and lower RANTES levels compared with all other groups or relatives (p<0.05). Overall, immune function abnormalities were seen mainly in adult patients with FA, which likely reflects their disease-related progression, and in children with DC, which may be a feature of early-onset severe disease phenotype.

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Levels of human serum granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor under pathological conditions

Cited by 43 publications

References 25 publications

An epidemiologic study of early biologic effects of benzene in Chinese workers.

An epidemiologic study of early biologic effects of benzene in Chinese workers.

Granulocyte colony-stimulating factor preferentially stimulates proliferation of monosomy 7 cells bearing the isoform IV receptor

Immune status of patients with inherited bone marrow failure syndromes

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