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Haopeng Yang

Publications and source records attributed to Haopeng Yang.

2 recordsLinked to original sources
PubMed2026

A Patient-Derived Xenograft Repository Capturing Clinical and Molecular Heterogeneity of Large B-cell Lymphoma.

UNLABELLED: Large B-cell lymphomas (LBCL) are a clinically and molecularly diverse group of malignancies with a rapidly evolving therapeutic landscape that has introduced new areas of clinical need, such as post-CD19 chimeric antigen receptor T (CART19) progression. Patient-derived xenograft (PDX) models are an important tool for mechanistic studies and preclinical evaluation of new therapies and can be generated from a variety of clinical contexts that capture tumor-intrinsic resistance mechanisms. We therefore undertook a comprehensive effort to generate PDX models that encompass the molecular landscape of LBCLs and include important clinical scenarios for new drug development. Here, we describe the first 48 models within this publicly available repository, capturing the transcriptional and genetic subsets of LBCL. These models also include 23 generated from post-CART19 progression patient biopsies, which reproduce patterns of progression driven by CD19 mutation or expression loss, as well as tumor cell-intrinsic CART19 resistance that we validated in vivo. SIGNIFICANCE: Here, we describe X-LYMPH (Xenografts of Lymphoma), a publicly available and molecularly annotated PDX repository that captures the heterogeneity of LBCL. X-LYMPH includes models of CAR T-cell resistance, providing a shared foundation for mechanistic research and therapeutic development for lymphomas. See related commentary by Evgin and Steidl, p. 655.

Humans↗
PubMed2026

A bivalent molecular glue linking lysine acetyltransferases to oncogene-induced cell death.

Developing cancer therapies that induce specific death of malignant cells is critical for preventing relapse. Highly effective strategies, such as immunotherapy, exemplify this principle. Here, we provide the mechanistic basis for a small-molecule approach that leverages chemically induced proximity (CIP) to kill diffuse large B cell lymphoma, the most common non-Hodgkin lymphoma. We developed lysine acetyltransferase (KAT)-based TCIPs (transcriptional/epigenetic chemical inducers of proximity), or KAT-TCIPs, which redirect p300/CREB-binding protein (CBP) to activate cell-death networks repressed by the oncogenic driver BCL6. Our lead KAT-TCIP reprograms the epigenome to initiate apoptosis. The crystal structure of the chemically induced p300-BCL6 complex reveals how chance protein-protein interactions may be exploited to confer the potency and selectivity of KAT-TCIPs. Thus, oncogenic drivers can be co-opted to activate robust cell death. Consistent with their gain-of-function mechanism, TCIPs recruiting different transcriptional activators-p300, BRD4, or CDK9-produce distinct genomic responses, suggesting specialized therapeutic uses.

Humans↗