# Imaging Disease Heterogeneity and Response to Therapy in Myelofibrosis

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $620,650

## Abstract

PROJECT SUMMARY/ABSRACT
Myelofibrosis (MF) is a chronic, ultimately fatal hematologic malignancy characterized by progressive fibrosis of
bone marrow, leading to severe anemia, hepatosplenomegaly, and debilitating constitutional symptoms with
cachexia. Treatment options remain extremely limited because only one FDA-approved drug currently exists for
MF. This drug may reduce splenomegaly and constitutional symptoms but only minimally reduces fibrosis or
abundance of malignant HSCs, the primary drivers of disease. The inability to reverse fibrosis and the malignant
clone is a major reason for continued poor prognosis in MF with ∼40% five-year survival. Oncologists currently
rely on bone marrow biopsy and spleen size measured by physical examination or anatomic MRI to assess
disease status and response to therapy in MF. Although regarded as the gold standard for analyzing bone
marrow, biopsy has several fundamental limitations as a test for status of a disease known to have extensive
heterogeneity in different anatomic sites of hematopoietic marrow. Biopsy samples only a small volume of bone
marrow from a single site, the iliac crest. In patients with extensive fibrosis in bone marrow, biopsy frequently
recovers no tissue (“dry tap”), leaving patients and physicians with no information about bone marrow
composition and severity of disease. As an invasive, painful procedure, patients only tolerate a limited number
of bone marrow biopsies. Measurements of spleen volume are non-invasive and easy to perform but fail to
address the fundamental cause and site of pathology, progressive fibrosis in bone marrow. To advance pre-
clinical studies in pathophysiology of MF, drug development, and ultimately clinical oncology, we will investigate
quantitative bone marrow MRI as a biomarker for disease status and response to therapy. We will assess bone
marrow composition and architecture using clinically-approved MRI sequences for cellularity (fat/water, Dixon
method), diffusion of water (DWI), and macromolecular structure (magnetization transfer saturation, MTS). We
will analyze imaging data by parametric response mapping (PRM), which captures spatial and temporal changes
in imaging data from the same patient over multiple studies. PRM markedly improves detection of early effects
of therapy and predicts long-term outcome in patients with multiple types of malignancies. To advance bone
marrow MRI as an imaging biomarker in MF, we will accomplish the following aims: 1) Validate quantitative MRI
metrics for bone marrow in mouse models of MF; 2) Quantify response to established and investigational
therapies in mice with genetic driver mutations mirroring patients; and 3) Conduct a prospective initial clinical
trial using quantitative MRI to monitor response to therapy in MF. We expect this research to show that
quantitative bone marrow MRI detects response to therapy in MF, allowing non-invasive measurements of
disease heterogeneity and assessment of drugs to reverse...

## Key facts

- **NIH application ID:** 10131156
- **Project number:** 5R01CA238023-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gary D Luker
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $620,650
- **Award type:** 5
- **Project period:** 2019-03-12 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131156

## Citation

> US National Institutes of Health, RePORTER application 10131156, Imaging Disease Heterogeneity and Response to Therapy in Myelofibrosis (5R01CA238023-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10131156. Licensed CC0.

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