# Prevention of MGUS Progression to MM by Modulating the Bone Marrow Microenvironment

> **NIH NIH U54** · BAYLOR COLLEGE OF MEDICINE · 2024 · $261,630

## Abstract

PROJECT SUMMARY
 The long-term objective of this work is to determine the functional role of the bone marrow microenvironment
in regulating the plasma cell growth of monoclonal gammopathy of undetermined significance (MGUS), using
multiple MGUS mouse models to define reliable biomarkers. Our findings should form the basis for designing
novel treatment approaches to prevent MGUS progression to multiple myeloma (MM). MGUS is a precancerous,
but clonal condition with aberrant DNA changes in plasma cells (PC). The prevalence of MGUS increases with
age. It is 3.2% at 50 years but rises to 9% for those older than 85, suggesting that risk factors associated with
aging play an important role in MGUS development. MGUS may progress to smoldering multiple myeloma
(SMM) and/or to MM, requiring therapy. Therefore, it is particularly important to identify and subsequently target
the risk factors associated with MGUS progression. By studying MGUS mouse models and primary human
samples from MGUS patients, we have demonstrated that bone marrow cellular senescence related to aging,
iron metabolism, and increased DKK1 in MGUS plasma cells are linked to MGUS progression. We hypothesize
that changes in the bone marrow microenvironment (ME) alter gene expression of MGUS plasma cells and
induce both bone destruction and immunosuppression resulting in MGUS plasma cell proliferation and disease
escape from effective immune surveillance. We propose three specific aims to prove this hypothesis: (1)
determine the role of cellular senescence of ME in MGUS progression; (2) determine the role of DKK1 in
promoting MGUS progression in adoptive transgenic mice; and (3) determine cellular and molecular mechanisms
of MGUS progression. Our goal is to discover novel therapeutic approaches to prevent human MGUS
progression.

## Key facts

- **NIH application ID:** 10910169
- **Project number:** 5U54CA272691-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** FENGHUANG ZHAN
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $261,630
- **Award type:** 5
- **Project period:** 2023-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910169

## Citation

> US National Institutes of Health, RePORTER application 10910169, Prevention of MGUS Progression to MM by Modulating the Bone Marrow Microenvironment (5U54CA272691-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10910169. Licensed CC0.

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