# Identifying Molecular Signatures Underlying Preleukemic Clonal Expansion

> **NIH NIH F31** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $31,685

## Abstract

Project Summary
 Clonal expansion occurs when the progeny of a cell excessively increases in number. It plays a
crucial role in theearly phase of many hematopoietic disorders such as myeloproliferative disorders,
myelodysplastic syndromes, and leukemias. During disease genesis, clonal expansion is often initiated by
somatic mutations,which in turn allow the accumulation of additional molecular changes that lead to
disease progression. However, not all clonal expansions lead to blood disorders or leukemia. Recent
studies show that hematopoietic stem and progenitor cells (HSPCs) commonly exhibit clonal expansion
after bone marrow transplantation and in healthy elderly without any apparent disease. Little is known
about the differences between normal and preleukemic clonal expansion, particularly with respect to the
molecular events underlying their differences. The proposed research project will address the hypothesis
that preleukemic clonal expansion is associated with distinct gene expression and/or epigenetic
characteristics in addition to the known leukemia-associated mutations, such as Tet2 mutations. Clonal
expansion will be tracked using a genetic barcoding technology in Tet2 inducible knockout mice. Moreover,
the genetic barcoding technology is integrated with droplet-based single cell RNA-sequencing (scRNA-
seq) and with single cell assay for transposable accessible chromatin-sequencing (scATAC-seq) to identify
molecular events that are associated with the distinct clonal expansion. The identified molecular signatures
of pre-leukemic clonal expansion will be functionally tested using the dCas9-KRAB mouse model. The
proposed study compares cellular expansion across different clones to identify rare cellular and molecular
events associated with Tet2-induced pre-leukemic clonalexpansion. These experiments will reveal the key
molecular drivers that trigger preleukemic clonal expansion undetectable using conventional assays of bulk
cell populations. The findings will help improve diagnosis of hematopoietic diseases, particularly TET2
related diseases, and may identify new therapeutic targets for their treatments.

## Key facts

- **NIH application ID:** 10390165
- **Project number:** 1F31HL149278-01A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Charles Bramlett
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $31,685
- **Award type:** 1
- **Project period:** 2022-02-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390165

## Citation

> US National Institutes of Health, RePORTER application 10390165, Identifying Molecular Signatures Underlying Preleukemic Clonal Expansion (1F31HL149278-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10390165. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*