{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE296nnn/GSE296649/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE296649"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Clonal evolution permits outgrowth of chemoresistant LMPP-like early progenitors in relapsed NPM1c AML [scRNA-Seq]","description":"The most recurrent acute myeloid leukemia (AML) driver in adult patients is a DNA frameshift insertion in the Nucleophosmin 1 (NPM1) gene. This mutation causes a translocation of the coding protein from the nucleus to the cytoplasm (NPM1c). We have generated paired single-cell multi-omics profiles for ~205,000 bone marrow cells collected from NPM1c AML patients at diagnosis and relapse. Detailed single-cell clonal analysis unveiled the evolution, expansion, and concomitant phenotypic changes of pathogenic AML (sub)clones. Blasts with an internal tandem duplication in the FLT3 gene (FLT3-ITD+ blasts) were often lowly abundant at diagnosis but expanded drastically at relapse at the expense of other blasts. Intriguingly, genetically identical FLT3-ITD+ blasts switched from granulocyte-monocyte progenitor-like at diagnosis toward more immature lympho-myeloid primed progenitor (LMPP)-like blasts at relapse. Our data shows that clonal evolution and the accumulation of a FLT3-ITD, is a key evolutionary event that alters AML blast plasticity with minimal changes in the blast phenotype. Increased plasticity favors the specific selection and expansion of FLT3-ITD+ blasts, which adopt a unique LMPP-like phenotype. The overriding transition between diagnosis and relapse suggests that therapeutic interventions (against proliferating cells) could license or accelerate this shift, highlighting the need for a tailored drug composition to target relapsed NPM1c AML.","dates":{"publication":"2026/05/01"},"accession":"GSE296649","cross_references":{"GSM":["GSM8974228","GSM8974227","GSM8974229","GSM8974220","GSM8974222","GSM8974221","GSM8974224","GSM8974223","GSM8974226","GSM8974225","GSM8974196","GSM8974195","GSM8974239","GSM8974238","GSM8974198","GSM8974231","GSM8974230","GSM8974197","GSM8974233","GSM8974232","GSM8974199","GSM8974235","GSM8974234","GSM8974237","GSM8974236","GSM8974240","GSM8974206","GSM8974205","GSM8974249","GSM8974208","GSM8974207","GSM8974209","GSM8974242","GSM8974241","GSM8974244","GSM8974200","GSM8974243","GSM8974202","GSM8974246","GSM8974201","GSM8974245","GSM8974204","GSM8974248","GSM8974247","GSM8974203","GSM8974251","GSM8974250","GSM8974217","GSM8974216","GSM8974219","GSM8974218","GSM8974252","GSM8974211","GSM8974210","GSM8974213","GSM8974212","GSM8974215","GSM8974214"],"GPL":["18573","24676"],"GSE":["296649"],"taxon":["Homo sapiens"]}}