# Synergistic role of signaling and epigenetics in leukemic transformation

> **NIH NIH R35** · SLOAN-KETTERING INST CAN RESEARCH · 2024 · $1,008,900

## Abstract

PROJECT ABSTRACT
We propose to use single cell studies of clinical isolates to explicate how mutations and differentiation status
coordinately regulate cell state, clonal expansion and malignant transformation. We will model sequential
activation/inactivation of somatic mutations in defined cell compartments and perform functional studies to
uncover critical gene networks and therapeutic dependencies. This will include single cell studies in primary
patient samples, use of innovative models which allow for sequential mutational activation/inactivation, and
functional genomic approaches to delineate mechanisms of transformation and novel therapeutic dependencies.
Moreover, we will delineate crosstalk between different cell types in normal and malignant hematopoiesis and
how these interactions impact therapeutic response. These tools will be distributed widely to enable studies of
tissue development/homeostasis, cell state changes, transformation, and therapeutic dependencies.

## Key facts

- **NIH application ID:** 10889256
- **Project number:** 5R35CA197594-09
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Ross L Levine
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,008,900
- **Award type:** 5
- **Project period:** 2017-01-17 → 2030-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10889256

## Citation

> US National Institutes of Health, RePORTER application 10889256, Synergistic role of signaling and epigenetics in leukemic transformation (5R35CA197594-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10889256. Licensed CC0.

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