{"database":"GEO","file_versions":[],"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=GSE268003"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"AML-PDXs Accelerate Development of Novel Drug Combinations for KMT2A-rearranged Acute Myeloid leukemia","description":"In pediatric acute myeloid leukemia (AML) the achievement of complete remission with standard treatments is obtained in most cases, but relapse still occurs in 30% of patients with greater incidence found in those patients showing high-risk AML genetic features. There is, therefore, an urgent need to identify novel effective therapies for children with relapsed-refractory leukemia. We established 26 AML patient-derived xenografts (PDXs), through sequential engraftment in NSG mice, including 14 high-risk genetic subtypes. Results confirmed AML-PDXs robustly resemble the original AML in terms of immunophenotype, genomic, and transcriptomic profiles, offering a comprehensive view of the disease complexity, useful to tailor therapies. In particular, by whole-exome sequencing, we evidenced a high intra-tumoral heterogeneity and we identified variants of each founder clone being perpetuated from patient-AML blasts to PDX. Then, we explored the efficacy of several drugs predicted to target these genomic variants in a three-dimensional in vitro culture and demonstrated that targeting variants of theWnt/β-cateninpathway is a promising strategy to reduce AML subclone fitness. By RNA-sequencing we observed thatKMT2A-rearranged AML and AML-PDXs shared aberrantly activated metabolic and stem expression signatures and documented that both IACS-010759 and Asparaginase, tailored to target transcriptome aberrancies, if combined with Venetoclax, mediated a significantly prolonged PDXs survival compared to Venetoclax used as single agent. Overall, our data indicate that AML-PDX models are unique tools for capturing AML heterogeneity, offering the possibility to target cancer cells in their multiple aspects, this increasing the chance to fully eradicate leukemia cells.","dates":{"publication":"2026/04/09"},"accession":"GSE268003","cross_references":{"GSM":["GSM8283769","GSM8283766","GSM8283765","GSM8283768","GSM8283767","GSM8283773","GSM8283772","GSM8283775","GSM8283753","GSM8283774","GSM8283771","GSM8283770","GSM8283759","GSM8283758","GSM8283777","GSM8283755","GSM8283754","GSM8283776","GSM8283757","GSM8283779","GSM8283778","GSM8283756","GSM8283762","GSM8283783","GSM8283761","GSM8283764","GSM8283763","GSM8283780","GSM8283760","GSM8283782","GSM8283781"],"GPL":["24676"],"GSE":["268003"],"taxon":["Homo sapiens"],"PMID":["[41576348]"]}}