GSE110898 Enhancer remodeling overcomes therapeutic resistance driven by epigenetic evolution in cancer HiChIP

Contributors : Mark A Dawson ; Charles C Bell ; Enid Y LamSeries Type : OtherOrganism : Mus musculusThe prevailing model of therapeutic resistance in cancer posits that malignant cells acquire genetic mutations in the context of therapeutic pressure that negate the efficacy of the drug. This mutation centric view of therapeutic resistance has recently been challenged by emerging evidence that shows a paucity of genetic diversity in malignant cells that evade therapeutic challenge emphasizing the role of epigenetic evolution in drug resistance. We have previously established that therapeutic resistance emerges in the absence of genetic adaptation from leukemia stem cells and whilst the clinical relevance of these findings has been established, what remains unanswered is whether transcriptional programs that confer resistance to therapies are pre-existing or acquired. It is also unclear how stable this adaptive transcriptional response is and whether it can be reversed. Here, we utilize a unique leukaemia model to highlight the key principles of epigenetic resistance. Using single cell RNA-seq with indexed flow sorting, we demonstrate that a form of Lamarckian evolution, namely transcriptional plasticity, drives epigenetic resistance. With a CRISPR-Cas9 screen we identify reciprocal regulators of the enhancer modification H3K4me1/2, LSD1 and MLL4, as important modulators of the resistant cell state. Knockdown or catalytic inhibition of LSD1 causes reversion to a drug sensitive ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Other Mus musculus Source Type: research

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Abstract INTRODUCTION: A pandemic coronavirus, SARS-CoV-2, causes COVID-19, a potentially life-threatening respiratory disease. Patients with cancer may have compromised immunity due to their malignancy and/or treatment, and may be at elevated risk of severe COVID-19. Community transmission of COVID-19 could overwhelm health care services, compromising delivery of cancer care. This interim consensus guidance provides advice for clinicians managing patients with cancer during the pandemic. MAIN RECOMMENDATIONS: During the COVID-19 pandemic: In patients with cancer with fever and/or respiratory symptoms, consid...
Source: Med J Aust - Category: General Medicine Authors: Tags: Med J Aust Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion A great deal of progress is being made in the matter of treating aging: in advocacy, in funding, in the research and development. It can never be enough, and it can never be fast enough, given the enormous cost in suffering and lost lives. The longevity industry is really only just getting started in the grand scheme of things: it looks vast to those of us who followed the slow, halting progress in aging research that was the state of things a decade or two ago. But it is still tiny compared to the rest of the medical industry, and it remains the case that there is a great deal of work yet to be done at all...
Source: Fight Aging! - Category: Research Authors: Tags: Of Interest Source Type: blogs
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Source: Life Sciences - Category: Biology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research
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Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
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Source: Hematology Oncology and Stem Cell Therapy - Category: Cancer & Oncology Source Type: research
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Source: Immunology Letters - Category: Allergy & Immunology Authors: Tags: Immunol Lett Source Type: research
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