# A compass for those with relapsed leukemia after transplant

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2024 · $734,482

## Abstract

ABSTRACT
Relapse of leukemia occurs in nearly half of patients after hematopoietic cell transplantation (HCT). While there
are a growing number of therapeutic options for leukemic relapse after HCT, we lack a clinical assay capable of
simultaneously detecting disease and triaging patients to treatment which will most likely benefit them. In this
application, we propose to rigorously evaluate and employ novel single-cell genomic methods and their
accompanying computational approaches to detect disease at low levels, inform mechanisms of relapse, and
direct future therapy. In Aim 1, we will optimize computational methods for detecting natural genetic variation
between donor and recipient, a diagnostic maneuver we believe will improve the sensitivity of detecting malignant
cells after HCT. We will then validate these methods using samples from patients in a retrospective fashion. To
provide insight into mechanisms of relapse, we have developed a novel molecular approach for identifying
perturbations in HLA and related genes, a common means by which leukemia evades the immune system after
HCT. In Aim 2, we will validate this method in a manner that explores the lower limit of detection for HLA-
perturbed cells. Finally, in Aim 3, we will build on decades of work using flow cytometry to assess the
heterogeneity of myeloid neoplasms by integrating our single-cell molecular measures with cell-surface
immunophenotype. Using this approach, we seek to define common molecular signatures in leukemia-initiating
cells (LICs), a subset of cells in myeloid neoplasms thought to be a chemo-resistant reservoir of leukemia. The
proposed studies will establish a new method for surveillance of residual disease after HCT, which we believe
will provide a deeper level of confidence and insight into leukemic relapse post-transplant. We expect these
studies to form the foundational preclinical data for a single-cell genomics clinical assay capable of risk-stratifying
patients with early evidence of leukemic relapse after HCT.

## Key facts

- **NIH application ID:** 10860489
- **Project number:** 1R01CA289886-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Scott Nicholas Furlan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $734,482
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860489

## Citation

> US National Institutes of Health, RePORTER application 10860489, A compass for those with relapsed leukemia after transplant (1R01CA289886-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10860489. Licensed CC0.

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