# The role of clonal hematopoiesis in the development and therapy of myeloid malignancies

> **NIH NIH R35** · DANA-FARBER CANCER INST · 2024 · $954,038

## Abstract

PROJECT SUMMARY
Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-associated condition in which a
clonal, somatic mutation that is associated with myeloid malignancies is detectable in the peripheral blood at a
variant allele fraction of at least 2%. Commonly mutated genes include the DNMT3A, TET2, and ASXL1
genes, all of which are present in myeloid malignancies and are commonly acquired early in the genetic
ontogeny of these cancers. Individuals with CHIP do not have a hematologic malignancy or altered blood
counts, but have a 10 to 50-fold increased risk of progression to hematologic malignancy, depending on the
size of the clone and the specific somatic mutation. We propose to examine the biology of individual mutations
and to understand cell-autonomous and cell non-autonomous mechanisms of clonal dominance. We will
examine progression from CHIP to malignancy and the ongoing addiction of the malignant cells to the truncal
mutations, thereby validating these mutations as therapeutic targets. We will integrate these biological studies
with large-scale genetic studies to examine the risk of malignant transformation and clinical consequences of
specific mutations. Finally, in the context of solid tumors, we will examine how CHIP generates tumor-
infiltrating macrophages with aberrant function, and how these somatically mutated macrophages influence
solid tumor biology, immune response, and response to immunotherapy.

## Key facts

- **NIH application ID:** 10892802
- **Project number:** 5R35CA253125-05
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Benjamin Levine Ebert
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $954,038
- **Award type:** 5
- **Project period:** 2020-08-15 → 2024-11-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892802

## Citation

> US National Institutes of Health, RePORTER application 10892802, The role of clonal hematopoiesis in the development and therapy of myeloid malignancies (5R35CA253125-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10892802. Licensed CC0.

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