Ludwig Cancer Research

Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling

Abstract Myeloproliferative neoplasms (MPN) are driven by the oncoproteins JAK2V617F, mutant calreticulin (CALR), and mutant thrombopoietin receptor (TPOR; MPL), all of which activate JAK/STAT signaling. While JAK2 signaling is engaged in all MPNs, TYK2 is dispensable for JAK2V61...

Clinical evaluation of AI-assisted quantitative marrow fibrosis assessment using Continuous Indexing of Fibrosis (CIF)

Abstract Assessment of fibrosis is central to the evaluation of diagnostic bone marrow trephine (BMT) biopsies. However, manual fibrosis grading is subjective and only semi-quantitative. We evaluated the clinical utility of a previously developed AI-based quantitative fibrosis as...

Dual-oxygen pancreatic cancer organoids recapitulate basal–classical heterogeneity validated by spatial transcriptomics

Pancreatic ductal adenocarcinoma (PDAC) comprises heterogeneous classical and basal-like subtypes. Although pancreatic cancer organoids (PCOs) are widely used, normoxic cultures preferentially maintain the classical subtype, limiting their ability to represent intrinsic intratumo...

Identifying phenotype-genotype-function coupling in 3D organoid imaging using Shape, Appearance and Motion Phenotype Observation Tool (SPOT)

Abstract Live cells in tissue are plastic, phenotypically dynamic, and modify their function in response to genetic and environmental perturbations. To unleash the power of live-cell imaging to identify phenotype-genotype-function coupling over time, we report the development of...