AI Article Synopsis
- * About 32.9% of patients had at least one mutation, with NOTCH1 and NF1 being the most frequently affected genes, although having clonal changes didn't significantly impact response to immunosuppressive treatment (IST).
- * Patients with shorter telomere lengths (TL) had worse responses to IST; TL can be a useful biomarker for treatment outcomes, where those with TL >5.9 had better IST response rates.
Article Abstract
We investigated the frequencies of cytogenetic aberrations and somatic mutations of prognostic relevance in 393 patients with aplastic anaemia (AA). Clonality was determined by G-banding/fluorescence in situ hybridization (FISH) (n = 245), and targeted capture sequencing was performed for 88 haematopoiesis-related genes (n = 70). The telomere length (TL) of bone marrow nucleated cells was measured at the single cell level by FISH (n = 135). Eighteen (4·6%) patients showed disease progression, and monosomy 7 (50·0%) was the most predominant cytogenetic evolution at disease transformation. One third of patients (32·9%) presented at least 1 mutation; the most frequently mutated genes were NOTCH1, NF1, SCRIB, BCOR and DNMT3A. The patient group with clonal changes (30·7%) showed an adverse response to immunosuppressive treatment (IST), compared to the non-clonal group, but this finding did not show statistical significance. The TL of AA patients was significantly shorter than normal control and patients with clonal changes showed significantly shorter TLs. Patients with TL>5·9 showed a higher response rate to IST (P = 0·048). In conclusion, the patients with clonal changes or TL attrition showed a poor response to IST. Shorter TL can be used not only as a biomarker, but also as a predictive marker for treatment response to IST.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/bjh.14691 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Epigenetic regulation of vascular smooth muscle cell phenotypes in atherosclerosis.
Atherosclerosis
December 2024
Section of Cardiorespiratory Medicine, University of Cambridge, VPD Heart and Lung Research Institute, Papworth Road, Cambridge Biomedical Campus, Cambridge, CB2 0BB, UK. Electronic address:
Vascular smooth muscle cells (VSMCs) in adult arteries maintain substantial phenotypic plasticity, which allows for the reversible cell state changes that enable vascular remodelling and homeostasis. In atherosclerosis, VSMCs dedifferentiate in response to lipid accumulation and inflammation, resulting in loss of their characteristic contractile state. Recent studies showed that individual, pre-existing VSMCs expand clonally and can acquire many different phenotypes in atherosclerotic lesions.
View Article and Find Full Text PDFCancer memory as a mechanism to establish malignancy.
Biosystems
December 2024
Interdisciplinary Center for Neurosciences, Heidelberg University, Im Neuenheimer Feld 366, 69120, Heidelberg, Germany. Electronic address:
Cancers during oncogenic progression hold information in epigenetic memory which allows flexible encoding of malignant phenotypes and more rapid reaction to the environment when compared to purely mutation-based clonal evolution mechanisms. Cancer memory describes a proposed mechanism by which complex information such as metastasis phenotypes, therapy resistance and interaction patterns with the tumor environment might be encoded at multiple levels via mechanisms used in memory formation in the brain and immune system (e.g.
View Article and Find Full Text PDFStochastic modeling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.
Cell Syst
December 2024
National Library of Medicine (NLM), National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address:
Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present a formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data.
View Article and Find Full Text PDFSpatiotemporal Profiling Defines Persistence and Resistance Dynamics During Targeted Treatment of Melanoma.
Cancer Res
December 2024
The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States.
Resistance of BRAF-mutant melanomas to targeted therapy arises from the ability of cells to enter a persister state, evade treatment with relative dormancy, and repopulate the tumor when reactivated. A better understanding of the temporal dynamics and specific pathways leading into and out of the persister state is needed to identify strategies to prevent treatment failure. Using spatial transcriptomics in patient-derived xenograft models, we captured clonal lineage evolution during treatment.
View Article and Find Full Text PDFNutrient colimitation is a quantitative, dynamic property of microbial populations.
Proc Natl Acad Sci U S A
December 2024
Department of Environmental Systems Science, Swiss Federal Institute of Technology (ETH) Zurich, Zurich 8006, Switzerland.
Resource availability dictates how fast and how much microbial populations grow. Quantifying the relationship between microbial growth and resource concentrations makes it possible to promote, inhibit, and predict microbial activity. Microbes require many resources, including macronutrients (e.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!