# Mapping cancer micro-environments for acute leukemia

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $455,428

## Abstract

While much is known about the cell-intrinsic factors that support leukemia progression, little is
understood about the role of the microenvironment. T cell acute lymphoblastic leukemia (T-ALL) cells
have commonly acquired mutations in pathways downstream of surface receptors that regulate
differentiation, survival and proliferation in response to environmental cues, and it is unknown whether
such genetic events free T-ALL from dependence on a putative leukemic niche. We have found that T-
ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Moreover, both
genetic targeting of the CXCL12 receptor CXCR4 in murine disease models and pharmacologic
CXCR4 antagonism in human T-ALL xenografts led to rapid and sustained disease remission. Here,
we propose to further map and functionally dissect the bone marrow niche for T-ALL, and test the
potential of targeting T-ALL:niche interactions as a novel therapeutic avenue for this aggressive blood
malignancy. We will use a combination of novel genetic reporters marking distinct niche elements and
targeted alleles of factors that have been implicated in T-ALL progression – CXCL12, Notch ligands,
and the cytokine IL-7 – to identify the key cells that maintain T-ALL. We will also use a potent CXCR4
antagonist and a panel of well-characterized primary human xenografts to test the therapeutic
potential of dislodging T-ALL cells from their niches.

## Key facts

- **NIH application ID:** 9991816
- **Project number:** 5R01CA202025-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Iannis Aifantis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $455,428
- **Award type:** 5
- **Project period:** 2016-09-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991816

## Citation

> US National Institutes of Health, RePORTER application 9991816, Mapping cancer micro-environments for acute leukemia (5R01CA202025-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9991816. Licensed CC0.

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