# Comprehensive dissection of the CLL genome & phenome to improve patient outcomes

> **NIH NIH P01** · DANA-FARBER CANCER INST · 2021 · $1,667,862

## Abstract

OVERALL ABSTRACT
Although we have made great strides in our understanding of the biology and treatment of chronic lymphocytic
leukemia (CLL) over the past decade, Richter's syndrome (RS) or the transformation of CLL to aggressive
lymphoma remains an area of unmet need in the clinical care of CLL patients. The challenges presented by RS
mandate large-scale interdisciplinary approaches to more completely link genomic and protein-level features
with cellular behavior so that more precise and sensitive molecular-based diagnostic schema and more effective
treatments for this devastating disease can be devised. Our hypothesis is that genomic and epigenomic
alterations define the trajectory from CLL to RS and that distinct subtypes of RS exist, leading to distinct
phenotypic behaviors. Our approach to address the challenge of understanding RS builds from the strengths
of our highly interactive and multi-disciplinary program in CLL research. Over the last funding period, we have
succeeded in generating the largest CLL `map' to date, integrating genetic, transcriptomic and methylome data
with clinical annotation from over 1000 CLL samples to discover clinically meaningful subtypes of disease and
novel driver alterations. From this information, we have also generated genetically-faithful CLL mouse models
reflective of human disease, defined patterns of disease kinetics and therapeutic resistance, and identified new
therapeutic vulnerabilities. Over the next 5 years, we will leverage the new resources generated by our Program,
ranging from computational to functional, genetic and phenotypic readouts, to confront the challenge of
understanding and addressing RS. Thus, our vision is that we will enact a precision approach for
understanding the distinct biology of disease transformation and the subtypes of disease, and perform functional
analyses of responses to small molecules and immunotherapy agents, that could be integrated and lead to a
paradigm shift in the detection and treatment for this disease. These highly translational initiatives are strongly
supported by the expertise of the Core Leaders. Our overarching goal is thus to revolutionize the clinical
outcomes of patients with this devastating disease and to utilize the information discovered from this Program to
motivate the rational design of the next generation of personalized and even curative therapies for RS.

## Key facts

- **NIH application ID:** 10270036
- **Project number:** 2P01CA206978-06
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Catherine Ju-Ying Wu
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,667,862
- **Award type:** 2
- **Project period:** 2016-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10270036

## Citation

> US National Institutes of Health, RePORTER application 10270036, Comprehensive dissection of the CLL genome & phenome to improve patient outcomes (2P01CA206978-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10270036. Licensed CC0.

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