{"doi":"10.3390/ijms262210818","title":"Molecular and Clinical Insights into TP53-Mutated MDS and AML","abstract":"<jats:p>TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprise a distinct subgroup of myeloid neoplasms with unique biological and clinical features. The molecular alterations linked to TP53 mutations drive genomic instability and treatment resistance and ultimately lead to poor survival outcomes. The disease biology is further shaped by alterations in immune response within the bone marrow microenvironment and significant changes in cellular metabolism. Conventional treatments, including chemotherapy and hypomethylating agents +/− venetoclax, offer limited benefit, with high relapse rates and short remissions. Allogeneic bone marrow transplantation is the only curative approach, but the vast majority of patients relapse. Novel therapeutic approaches—ranging from p53 reactivation strategies to immunotherapy and targeted inhibition of specific signaling pathways—are under active investigation. Our review summarizes current knowledge on the molecular pathogenesis, prognostic implications, and therapeutic landscape of TP53-mutated MDS/AML and discusses ongoing challenges and opportunities for improving patient outcomes.</jats:p>","journal":"International Journal of Molecular Sciences","year":2025,"id":596741,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":311492,"name":"Theodoros Karantanos","orcid":"0000-0002-6792-8298","position":1,"is_corresponding":false},{"id":1528419,"name":"Erotokritos Georgantzinos","orcid":"0009-0002-7377-0930","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Molecular and Clinical Insights into TP53-Mutated MDS and AML","abstract":"<jats:p>TP53-mutated myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) comprise a distinct subgroup of myeloid neoplasms with unique biological and clinical features. The molecular alterations linked to TP53 mutations drive genomic instability and treatment resistance and ultimately lead to poor survival outcomes. The disease biology is further shaped by alterations in immune response within the bone marrow microenvironment and significant changes in cellular metabolism. Conventional treatments, including chemotherapy and hypomethylating agents +/− venetoclax, offer limited benefit, with high relapse rates and short remissions. Allogeneic bone marrow transplantation is the only curative approach, but the vast majority of patients relapse. Novel therapeutic approaches—ranging from p53 reactivation strategies to immunotherapy and targeted inhibition of specific signaling pathways—are under active investigation. Our review summarizes current knowledge on the molecular pathogenesis, prognostic implications, and therapeutic landscape of TP53-mutated MDS/AML and discusses ongoing challenges and opportunities for improving patient outcomes.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41303305","pmcid":"PMC12652684","openalex_id":"https://openalex.org/W4415990948","authors":[],"funders":[{"funder_name":"NHLBI","grant_id":"K08HL168777","title":null},{"funder_name":"Leukemia Research Foundation New Investigator Research Grant Program","grant_id":"","title":null}],"total_grants":2,"fwci":1.7307,"citation_percentile":0.87066483,"influential_citations":0,"citation_trend":[{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/26/22/10818/pdf?version=1762507931","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/26/22/10818/pdf?version=1762507931","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/26/22/10818/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms262210818","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41303305","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12652684","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12652684?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Acute Myeloid Leukemia Research","Cancer-related Molecular Pathways","Chronic Myeloid Leukemia Treatments"],"mesh_terms":["Humans","Mutation","Myelodysplastic Syndromes","Prognosis","Leukemia, Myeloid, Acute","Tumor Suppressor Protein p53"],"keywords":["Myeloid leukemia","Immunotherapy","Myelodysplastic syndromes","Bone marrow","Disease","Myeloid","Immune system","Transplantation","Hypomethylating agent","Acute myeloid leukemia","Myelodysplastic syndrome","Targeted Therapy","P53 Activation","Tp53 Mutation","Clonal Hemopoiesis","Tp53 Mutated Mds/aml"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T11:08:08.999855Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}