# Inflammatory Disease Associations in Clonal Hematopoiesis

> **NIH NIH K08** · DANA-FARBER CANCER INST · 2024 · $165,080

## Abstract

Project Summary
Clonal hematopoiesis (CH) is the pre-malignant expansion of a population of blood cells derived from a single
hematopoietic stem cell and is often caused by somatic mutations in leukemia driver genes. CH has been
associated with significant clinical outcomes including hematologic cancers, various inflammatory
comorbidities, and increased all-cause mortality. Among individuals with CH, there is inconsistent penetrance
for inflammatory disease symptoms and risk of inflammatory disease varies widely. Reliable clinically-validated
models that estimate a patient’s risk of inflammatory disease outcomes and management strategies that
prevent or effectively overcome inflammatory disease outcomes in CH are major medical needs. The goal of
this proposal is to define and better understand the relationship between CH and inflammatory disease
outcomes. Aim 1 will define the association between CH and rheumatologic diseases and activities in Aim 2
will define the CH genotypes most powerfully linked to inflammatory phenotypes and generate a statistical
algorithm to estimate individual risk of inflammatory disease in patients with CH. Then, using a cohort of
patients with clonal cytopenia of uncertain significant (CCUS), a subtype of CH, who have been exposed to
hypomethylating agents (HMA), Aim 3 will explore the influence of HMA therapy on inflammatory disease
symptoms. Collectively, this work will enable the identification of patients with CH who are at risk for
inflammatory diseases and provide preliminary data to motivate future interventional clinical trials with
endpoints designed around prevention of inflammatory disease outcomes. Dr. Lachelle D. Weeks is a
hematologist and scientist at the Dana-Farber Cancer Institute (DFCI) and translational investigator in the
Division of Population Sciences within the Department of Medical Oncology at DFCI. She spends 80% of her
time in translational research and 20% in clinical practice caring for and counseling patients with CH and
myelodysplastic syndrome (MDS). In addition to her primary mentor, Dr. Weeks has established an advisory
committee of internationally recognized experts in CH, myeloid malignancies, clinical computational oncology,
and genetic epidemiology. Her research and career development activities will be conducted at DFCI which
has an outstanding research community and a long track record for successful mentorship of independent
scientists. This is an ideal environment for completion of the proposed research, execution of the proposed
career development strategy, and the ultimate realization of Dr. Weeks’s long-term career goal of becoming an
R01-funded physician-scientist.

## Key facts

- **NIH application ID:** 10982741
- **Project number:** 1K08HL171883-01A1
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Lachelle Dawn Weeks
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $165,080
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10982741

## Citation

> US National Institutes of Health, RePORTER application 10982741, Inflammatory Disease Associations in Clonal Hematopoiesis (1K08HL171883-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10982741. Licensed CC0.

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