# Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation

> **NIH NIH K01** · MEDICAL COLLEGE OF WISCONSIN · 2024 · $156,600

## Abstract

ABSTRACT
Myelodysplastic syndromes (MDS) are a heterogenous group of clonal hematopoietic stem cell disorders,
characterized by ineffective hematopoiesis and a tendency to progress to acute myeloid leukemia in 30% of
the patients. Currently the only curative therapy for MDS is allogeneic hematopoietic stem-cell transplantation
(HCT). However, the mortality after HCT is high due to relapsed disease and transplant-related complications.
The commonly used MDS prognostic models for HCT only consider non-genetic factors, thus could not
accurately predict the outcomes after HCT. Novel predictive markers are therefore critically needed to identify
patients who are most likely to benefit from HCT. Mitochondria play a critical role in hematopoietic cell
homeostasis and differentiation. Genetic and epigenetic alterations in mitochondrial DNA (mtDNA) can impair
mitochondrial functions and play a pathophysiological role in MDS. This Career Development Award will
provide training and research experience to Dr. Dong to support her long-term career goal of becoming an
independent investigator in integrative molecular epidemiology, with a focus on applying state-of-the-art
omics technologies and innovative population-based epidemiologic methods to reduce the burden of
hematologic diseases. While Dr. Dong has had comprehensive training in genetics and epidemiology, she
requires further training in methodologies of HCT-related outcomes and epigenetics. She has assembled a
mentoring team comprised of a primary mentor, Dr. Raul Urrutia, Director in the Genomic Sciences and
Precision Medicine Center and renowned leader in genomics, epigenomics and precise medicine; and two
co-mentors: Dr. Wael Saber, Professor and Scientific Director in the Acute and Chronic Leukemia Working
Committees in the CIBMTR specializing in HCT and MDS; Dr. Paul Auer, Professor and Cancer Center Core
Director with expertise in statistics and bioinformatics. Leveraging the existing whole genome sequencing
data from the “MDS Genomics and Epigenetics Study” in the CIBMTR, Dr. Dong will focus on mitochondrial
genome to address the research gaps mentioned above: 1) determine mitochondrial genomic landscape
associated with MDS outcomes after allo-HCT; 2) quantify mtDNA copy number and evaluate its associations
with MDS outcomes after HCT; and 3) identify mtDNA methylation profiles associated with MDS outcomes
after HCT. The findings will improve our understanding of MDS etiology and provide additional molecular
predictors of MDS outcomes after HCT to help developing individualized risk prediction and targeted
treatments.

## Key facts

- **NIH application ID:** 10830420
- **Project number:** 5K01HL164972-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Jing Dong
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $156,600
- **Award type:** 5
- **Project period:** 2023-04-20 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830420

## Citation

> US National Institutes of Health, RePORTER application 10830420, Prognostic implications of mitochondrial inheritance in myelodysplastic syndromes after stem-cell transplantation (5K01HL164972-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10830420. Licensed CC0.

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