# The role of inflammation in the regulation of immune response in acute myeloid leukemia

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $543,631

## Abstract

Project Summary/Abstract
Survival outcomes of acute myeloid leukemia (AML) patients are negatively affected by high inflammation in the
bone marrow compared to low inflammation patients within the same molecular subgroup. The overarching goal
of our study is to delineate functionally relevant contributors to aberrant inflammation, characterize changes to
the inflammatory state longitudinally during different standard-of-care treatment approaches and determine
whether targeting inflammation via inhibitors that target the crucial mediators of inflammation can improve
treatment response and survival. The proposal was prompted by our recent characterization of inflammation-
mediated progression to AML in animal models and the notable cooperation with select mutational backgrounds
to promote leukemogenesis; and our notion of distinct cellular remodeling of both leukemic cells and the
microenvironment to promote inflammation. We believe that the observed strong negative treatment response
and survival association that was independent from other genetic contributors provides an exciting rationale to
target aberrant inflammation in AML patients in order to improve treatment response and disease progression.
This goal will be achieved by two independent, but complementary Specific Aims. (1) Utilizing our large cohort
of 1,600 AML patients who were molecularly and clinically characterized and have a defined inflammatory state,
we will characterize those patients with the highest and the lowest inflammation and compare cell state, cell fate
and immune response at the single cell level via a comprehensive multi-omic approach. (2) We will track
dynamics of inflammatory, immune-regulatory and associated clonal structures during different treatments via
the same multi-omic profiling with an integrated approach that first profiles longitudinally collected patient
samples with select genotypes during different treatments, followed by patient derived xengraft models of the
same patients that will undergo 2 different therapeutic approaches followed by serial profiling, thereby allowing
for direct comparison and definitive characterization of the observed changes. Lastly, we will test the
effectiveness of anti-inflammatory agents (IL-1 inhibitors) to lower inflammation and prevent the inflammation-
associated bone marrow remodeling and inferior treatment response. Together, our results will, for the first time,
provide critically needed information to provide a basis for targeting aberrant inflammation in AML patients.

## Key facts

- **NIH application ID:** 10883702
- **Project number:** 5R01CA283574-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Iannis Aifantis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,631
- **Award type:** 5
- **Project period:** 2023-07-06 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10883702

## Citation

> US National Institutes of Health, RePORTER application 10883702, The role of inflammation in the regulation of immune response in acute myeloid leukemia (5R01CA283574-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10883702. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*