Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38254070", "kind": "science-record", "revision": 3, "content_hash": "sha256:3ec7a1fd460084a1edfb624b7b988c9a1185ed7794c6788f904b3d05bd86c3b3", "created_at": "2026-11-01T19:20:10Z", "updated_at": "2026-11-01T22:11:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.", "doi": "10.1186/s12885-024-11859-w", "pmid": "38254070", "authors": ["Chunlai Yin", "Yanqi Li", "Cheng Zhang", "Shizhu Zang", "Zilong Wang", "Xue Yan", "Tonghui Ma", "Xia Li", "Weiping Li"], "journal": "BMC cancer", "year": 2024, "abstract": "BACKGROUND: Myelodysplastic syndrome (MDS) is known to arise through the pathogenic bone marrow mesenchymal stem cells (MSC) by interacting with hematopoietic stem cells (HSC). However, due to the strong heterogeneity of MDS patients, it is difficult to find common targets in studies with limited sample sizes. This study aimed to describe sequential molecular changes and identify biomarkers in MSC of MDS transformation.\nMETHODS: Multidimensional data from three publicly available microarray and TCGA datasets were analyzed. MDS-MSC was further isolated and cultured in vitro to determine the potential diagnostic and prognostic value of the identified biomarkers.\nRESULTS: We demonstrated that normal MSCs presented greater molecular homogeneity than MDS-MSC. Biological process (embryonic skeletal system morphogenesis and angiogenesis) and pathways (p53 and MAPK) were enriched according to the differential gene expression. Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition. Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs.\nCONCLUSION: Our comprehensive study of gene expression profiling has identified dysregulated genes and biological processes in MSCs during MDS. HOXB3 and HOXB7 are proposed as novel surrogate targets for therapeutic and diagnostic applications in MDS.", "claims": [{"id": "claim-method", "statement": "The overall survival (OS) analysis of hub genes was conducted using the Kaplan-Meier curve in cBioPortal.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38254070", "locator": "sections[15] \"Survival analysis\" paragraph 2", "quote": "The overall survival (OS) analysis of hub genes was conducted using the Kaplan-Meier curve in cBioPortal."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly available in National Center for Biotechnology Information at https://www.ncbi.nlm.nih.gov/, with the reference number as GSE140101, GSE107490 and GSE61853. The OS analysis of hub genes was performed using the Kaplan-Meier curve in cBioPortal (http://www.cbioportal.org).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38254070", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "The data that support the findings of this study are openly available in National Center for Biotechnology Information at https://www.ncbi.nlm.nih.gov/, with the reference number as GSE140101, GSE107490 and GSE61853. The OS analysis of hub genes was performed using the Kaplan-Meier curve in cBioPortal (http://www.cbioportal.org)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "HOXB3 and HOXB7 were identified as progressively upregulated genes during the normal-MDS-AML transition, and blocking them in MSCs restored proliferation, differentiation, and hematopoietic support functions.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38254070", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Furthermore, we identified HOXB3 and HOXB7 as potential causative genes gradually upregulated during the normal-MDS-AML transition."}, {"asset": "source:pmid:38254070", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Blocking the HOXB3 and HOXB7 in MSCs could enhance the cell proliferation and differentiation, inhibit cell apoptosis and restore the function that supports hematopoietic differentiation in HSCs."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "HOXB3 and HOXB7 were identified as progressively upregulated genes during the normal-MDS-AML transition, and blocking them in MSCs restored proliferation, differentiation, and hematopoietic support functions.", "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:38254070"], "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:GSE107490"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "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:GSE107490"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38254070", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-024-11859-w", "sha256": "sha256:1c3158bcc123aa9422c706ee3bf05cb77ac87d690187fa15a945fd8be19edd47", "bytes": 46448, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12885-024-11859-w", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10802074", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE107490", "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=GSE107490", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE107490", "version": null, "note": "The data that support the findings of this study are openly available in National Center for Biotechnology Information at https://www.ncbi.nlm.nih.gov/, with the reference number as GSE140101, GSE107490 and GSE61853. 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