# Core 1: Lymphoma models

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $249,555

## Abstract

CORE 1 LYMPHOMA MODEL SYSTEMS: SUMMARY/ABSTRACT
The Lymphoma Model System core (LMSC) will assemble and characterize the reagents critical for this
proposal, including the vast array of engineered mouse models (GEMM), clinically and molecularly annotated
primary samples, patient-derived tumor xenograft (PDX), and PDX-derived cell models, as well as patient-
derived organoids (PDOs). These resources will be provided to project leaders to define the pathogenetic role
of selected lesions and to identify their relevance in the genesis and maintenance of Diffuse Large B-Cell
Lymphomas (DLBCL), taking advantage of innovative in-vitro and in-vivo platforms. We predict that the services
of the LMSC will provide the basis for the biological dissection of the genetic lesions described in all Projects,
leading to a deeper knowledge of how 3D genome organization plays a role in gene regulation and in oncogenic
transcriptional programs. We anticipate assembling a relatively large library of PDX representative of DLBCL
neoplasms carrying defects that impair chromatin organization and gene expression. To achieve these
objectives, we will integrate multiple platforms taking advantage of conventional morphology with a large battery
of antibodies and molecular-based approaches (WES, RNAseq, etc.) to define the natural evolution of lymphoid
elements carrying ad hoc defects, stratify the emerging neoplasms in PDX and humanized models and correlate
them with those detected in primary neoplasms. Importantly, primary 2D and 3D cultures and tumor xenografts
have been tested, showing that they essentially mimic the original patient tumor, including tumor heterogeneity,
and they can effectively predict response to therapies. Of note, models from primary patient-derived cultures or
PDX have proven to be more informative than conventional cell lines allowing precise determinations and more
reliable assessments. As many as 85% of drugs within in vitro activity in established cell lines have failed in
human studies, primarily because of a lack of efficacy in complex systems or human settings. Having decided to
interrogate defects that can be observed in unique/rare neoplasms and test the specific relationships between
host and lymphoma elements in young and older individuals, we will take advantage of the lentiviral-mediated
system to create ad hoc models (Project 3). Thus, our models are beneficial for in vivo mechanistic studies (all
projects). The information they provide will be instrumental in understanding the pathogenetic potential of the
defects investigated in this application, leading to potential targeted therapies (Projects 1, 3, and 4).

## Key facts

- **NIH application ID:** 10847992
- **Project number:** 1P01CA272295-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Giorgio Inghirami
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,555
- **Award type:** 1
- **Project period:** 2024-08-12 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10847992

## Citation

> US National Institutes of Health, RePORTER application 10847992, Core 1: Lymphoma models (1P01CA272295-01A1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10847992. Licensed CC0.

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