Distinguishing features of basophil and neutrophil activation by major basic protein

Thomas, Larry L.; Haskell, Michelle D.; Sarmiento, Emmanuel U.; Bilimoria, Yasmeen

doi:10.1016/0091-6749(94)90328-x

Cited by 10 publications

(2 citation statements)

References 25 publications

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“…Prominent genes upregulated from days 1 to 3 include those involved in neutrophil function (MPO, PRG2, TNFAIP6, MMP25), myeloid differentiation (CEBPE, RXRA, TYROBP), and leukocyte activation, as well as myeloid tumor suppressor activity (EGR1, MS4A3, CDKN1A/p21; Figure 3D; supplemental Table 19). [70][71][72][73][74][75][76] In addition, GSEA indicated that DAC treatment resulted in depletion of established HSC and LSC genes but enriched for myeloid differentiation genes (Figure 3E). We conclude that although DNA methylation is associated with many of the gene expression changes associated with BC reprogramming, the inability of DNMTis to reverse the majority of DNA methylation-associated gene expression changes, even under optimized in vitro conditions, suggests additional layers of epigenetic regulation in BC reprogramming.…”

Section: A Bc-specific Methylome Is Enriched For Prc Targets and Regulates Differentiationmentioning

confidence: 98%

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

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Lee

et al. 2020

Blood

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Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.

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Section: A Bc-specific Methylome Is Enriched For Prc Targets and Regulates Differentiationmentioning

confidence: 98%

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

Javed

Lee

et al. 2020

Blood

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“…Bone marrow proteoglycan acts as a cytotoxin and helminthotoxin; it causes activation and degranulation of neutrophils in a non-cytotoxic fashion [35,36], which is reflected in the enriched biological processes "neutrophil mediated immunity", "neutrophil activation involved in immune response", and "neutrophil degranulation". Bone marrow proteoglycan further leads to activation and aggregation of platelets [37], contributing to the enriched pathway "platelet degranulation".…”

Section: Discussionmentioning

confidence: 99%

Fox Serum Proteomics Analysis Suggests Host-Specific Responses to Angiostrongylus vasorum Infection in Canids

et al. 2021

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Dogs infected with the cardiopulmonary nematode Angiostrongylus vasorum may suffer from respiratory distress and/or bleeding disorders. Descriptions of clinical signs in foxes are rare, despite high prevalence. To evaluate the impact of infection on coagulation and immune response, serum proteins from eight experimentally infected foxes before and after inoculation (day 0, 35, 84, 154) were subjected to differential proteomic analyses based on quantitative data and compared to available data from dogs. The number of proteins with differential abundance compared to the uninfected baseline increased with chronicity of infection. Bone marrow proteoglycan, chitinase 3-like protein 1 and pulmonary surfactant-associated protein B were among the most prominently increased proteins. The abundance of several proteins involved in coagulation was decreased. Enriched pathways obtained from both increased and decreased proteins included, among others, “platelet degranulation” and “haemostasis”, and indicated both activation and suppression of coagulation. Qualitative comparison to dog data suggests some parallel serum proteomic alterations. The comparison, however, also indicates that foxes have a more adequate immunopathological response to A. vasorum infection compared to dogs, facilitating persistent infections in foxes. Our findings imply that foxes may be more tolerant to A. vasorum infection, as compared to dogs, reflecting a longer evolutionary host–parasite adaptation in foxes, which constitute a key wildlife reservoir.

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Comparative Structure, Proximal Promoter Elements, and Chromosome Location of the Human Eosinophil Major Basic Protein Genes

et al. 2001

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Distinguishing features of basophil and neutrophil activation by major basic protein

Cited by 10 publications

References 25 publications

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia

Fox Serum Proteomics Analysis Suggests Host-Specific Responses to Angiostrongylus vasorum Infection in Canids

Comparative Structure, Proximal Promoter Elements, and Chromosome Location of the Human Eosinophil Major Basic Protein Genes

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