Implication of therapeutic outcomes associated with molecular characterization of paediatric aplastic anaemia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33490648", "kind": "science-record", "revision": 8, "content_hash": "sha256:d850faf20fcad6fa9f775f004cd82e09a48853834d7e669c14092cafd8cf5cb1", "created_at": "2026-11-01T15:41:23Z", "updated_at": "2026-11-01T22:03:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Implication of therapeutic outcomes associated with molecular characterization of paediatric aplastic anaemia.", "doi": "10.1016/j.bbrep.2020.100899", "pmid": "33490648", "authors": ["Sarmistha Adhikari", "Kaustav Nayek", "Arghya Bandyopadhyay", "Paramita Mandal"], "journal": "Biochemistry and biophysics reports", "year": 2021, "abstract": "OBJECTIVES: Severe aplastic anemia is characterized by a hypocellular bone marrow and peripheral cytopenia. Mesenchymal stem cells (MSCs) play a crucial role in haematopoietic stem cells (HSCs) development and the development of microenvironment suitable for hematopoiesis. Molecular characterization of telomere maintenance pathway and gene expression profiling of MSCs can be important for the therapeutic interventions among paediatric aplastic anaemia patients.\nMETHODS: The study involved paediatric aplastic anaemia patients (n = 10) and age matched paediatric healthy donors (n = 8). Peripheral blood samples were collected from the individuals. Average leucocyte telomere length and gene expression of the telomere maintenance genes were determined by quantitative real time PCR. Microarray based gene expression profiles (GSE33812) of MSCs for five paediatric aplastic anaemia patients were analyzed compared to five healthy controls and the data was downloaded from the GEO database.\nRESULTS: The telomere length was significantly shorter among paediatric AA patients compared to age matched healthy donors. Interestingly, one subgroup (n = 2) of paediatric AA patients has moderate telomere length comparable to age matched healthy donors. Based on the gene expression analysis of telomere maintenance pathway, TERF2 was significantly downregulated among paediatric patients with shorter telomere length but not among paediatric patients with moderate telomere length. Gene expression profiling of MSCs revealed three differentially expressed genes (GAS2L3, MK167 and TMSB15A) among the patients and was associated with therapeutic outcome.\nCONCLUSION: Telomere length estimation and gene expression patterns of the MSCs and telomere length maintenance pathway may serve as a potential biomarker and could be associated with therapeutic choice of paediatric aplastic anaemia patients.", "claims": [{"id": "claim-method", "statement": "Non-parametric two sample Mann Whitney U test was used to identify association of disease categories and healthy donors with variables that did not follow normal distribution.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33490648", "locator": "sections[9] \"Statistical analysis\" paragraph 2", "quote": "Non-parametric two sample Mann Whitney U test was used to identify association of disease categories and healthy donors with variables that did not follow normal distribution."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The expression analysis of the microarray datasets from the Gene Expression Omnibus [GEO] database with accession id GSE33812 [29] of the National Center for Biotechnology Information [NCBI] of the U.S. National Library of Medicine was used for the current study. There was single gene expression profiling dataset for aplastic anemia patients among children. This dataset included 5 severe paediatric aplastic anemia patients compared to 5 healthy donors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33490648", "locator": "sections[8] \"Gene expression profiling of MSCs\" paragraph 2", "quote": "The expression analysis of the microarray datasets from the Gene Expression Omnibus [GEO] database with accession id GSE33812 [29] of the National Center for Biotechnology Information [NCBI] of the U.S. National Library of Medicine was used for the current study. There was single gene expression profiling dataset for aplastic anemia patients among children. This dataset included 5 severe paediatric aplastic anemia patients compared to 5 healthy donors."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33490648"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE33812"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_mann_whitney", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE33812"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_mann_whitney"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33490648", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.bbrep.2020.100899", "sha256": "sha256:bd8e3604221724079b2278228811e7f1bc89cebe562b362acd719ab4522720a6", "bytes": 27803, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.bbrep.2020.100899", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7809188", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE33812", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE33812", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE33812", "version": null, "note": "The expression analysis of the microarray datasets from the Gene Expression Omnibus [GEO] database with accession id GSE33812 [29] of the National Center for Biotechnology Information [NCBI] of the U.S. National Library of Medicine was used for the current study. 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["Aplastic Anemia Patients", "", "5", "11.6 (10–14.7)", "Immunosuppressive therapy, Haematopoietic stem cell transplantation"], ["Aplastic Anemia Patients", "Aplastic Anemia Patients with immunosuppressive therapy", "3", "11.6 (10–12.2)", "Recovery after immunosuppressive therapy"], ["Aplastic Anemia Patients with bone marrow transplantation therapy", "2", "13 (11.3–14.7)", "Recovery after Haematopoietic stem cell transplantation"], ["Healthy Donors", "", "5", "15 (2.8–17.8)", "Nil"]], "row_count": 5, "column_count": 5, "numeric_cells": 8, "header_rows": 1, "locator": "section[8]/table-wrap[1]#tbl2"}}, {"id": "asset:table:pmid:33490648:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6a3868514149d6900877f4b224ab6141c374845f874fe5d2d791c7beaa79a41c", "bytes": 1072, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#tbl3", "version": null, "note": "Differentially downregulated genes among paediatric patients with aplastic anaemia compared to healthy donors.", "structure": {"pmcid": "PMC7809188", "section_index": 13, "section_title": "Gene expression profiling of MSCs revealed characteristic molecular differences among the subtypes of paediatric aplastic anaemia", "row_count": 5, "column_count": 8}, "table": {"label": "Table 3", "caption": "Differentially downregulated genes among paediatric patients with aplastic anaemia compared to healthy donors.", "rows": [["Patient 1_log fold change", "Patient 2_log fold change", "Patient 3_log fold change", "Patient4_log fold change", "Patient 5_log fold change", "Gene", "Gene name", "Remarks"], ["−2.144", "−2.524", "−2.97", "−2.841", "−2.535", "AGT", "angiotensinogen", "Universally downregulated among all patients"], ["−1.048", "−2.275", "−2.343", "−4.192", "−2.003", "GAS2L3", "growth arrest specific 2 like 3", "Differentially downregulated among patients with 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