GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE313nnn/GSE313901/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313901GEOGSEfalseSPINK2 silencing suppresses leukemic proliferation and restores myeloid commitment via MECOM downregulation in acute myeloid leukaemiaMyeloid leukaemias harboring complex karyotypes present several unrelated cytogenetic abnormalities and form a distinct subset of AML linked to a dismal prognosis. Currently, no effective options are available for the treatment of those patients, and the discovery of novel therapeutic strategies represent an urgent clinical priority. We previously developed a bioinformatic framework for the identification of novel molecular vulnerabilities for disease stratification and treatment and observed SPINK2, a serine protease inhibitor Kazal-type 2, as a novel and promising candidate target in AML, with particularly pronounced effect in complex karyotype patients. Using publicly available bulk and single cell RNA-seq datasets, we discovered a robust association between SPINK2 and cell cycle regulators, most notably S-phase genes. By performing shRNA-mediated genetic manipulation of SPINK2 expression in a complex karyotype AML cell lines, we marked a profound impairment of proliferation coupled with an induction of terminal myeloid commitment. Moreover, SPINK2-deficient FUJIOKA cells revealed a significant correlation between SPINK2 and MECOM expression, consistent with findings in patients harbouring complex karyotypes, yet absent in other AML subsets from the TARGET-AML cohort. Our findings suggest a novel potential correlation between SPINK2 and MECOM expression in complex karyotype leukemias and warrant further investigation into the underlying molecular mechanisms through which the SPINK2-MECOM axis enforces aberrant self-renewal and the development of novel targeted approaches aimed at modulating its expression in complex karyotypic AML.2026/04/08GSE313901GSM9377472GSM9377473GSM9377474GSM9377475GSM9377471GSM937747624676313901Homo sapiens[41776172]