# Extracellular DNA in regulation of multiple myeloma

> **NIH NIH R01** · WISTAR INSTITUTE · 2020 · $427,973

## Abstract

Abstract
Multiple myeloma (MM) is a devastating bone marrow (BM) cancer that remains uniformly fatal
despite the emergence of novel therapeutics. The tumor microenvironment promotes tumor
growth and resistance to chemotherapy through poorly understood interactions between tumor
cells and the surrounding BM cells. Our preliminary data demonstrates that a population of BM
mature and immature neutrophils is involved in the regulation of MM chemoresistance. In
response to MM-derived soluble factors, neutrophils can release DNA. This extracellular cell-free
DNA induces the chemoresistance of MM cells, possibly through activation of IRE1/XBP1
pathway of the unfolded protein response (UPR). The goal of this proposal is to determine the
molecular mechanism responsible for cell-free DNA mediated chemoresistance in MM cells and to
develop an approach to target it. By targeting of this novel chemoresistance mechanism we hope
to improve chemotherapy responses and thereby improve MM outcomes. The following specific
aims will be addressed:
Specific Aim 1. Identify the mechanisms and clinical relevance of DNA release by neutrophils in
MM.
Specific Aim 2. Determine the mechanisms of cell-free DNA effect on MM cells.
Specific Aim 3. Determine the role of the UPR in cell-free DNA mediated MM chemoresistance.

## Key facts

- **NIH application ID:** 9982212
- **Project number:** 5R01CA196788-05
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Yulia Nefedova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $427,973
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982212

## Citation

> US National Institutes of Health, RePORTER application 9982212, Extracellular DNA in regulation of multiple myeloma (5R01CA196788-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982212. Licensed CC0.

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