# Characterizing stem cell-like B cell subpopulations and dissecting their role in tumorigenesis

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $391,699

## Abstract

One third of B-cell lymphoma patients relapse and remain incurable despite effective targeted
therapies. Although, the serially relapsing nature of these tumors support the presence of stem-
like lymphoma repopulating cells, this notion remains controversial and underexplored.
Resistance to this concept arise from the fact that -in contrast to leukemia or other solid tumors
that originate from stem-like cells- most lymphomas arise from fully differentiated, mature B cells.
However, our preliminary studies provide strong evidence for the existence of rare subpopulations
of B-cells undergoing antigen-activation (in response to pathogens) with stem-like molecular
features and functional properties in a T-cell dependent manner. Moreover, we found that specific
lymphoma-associated mutations further enhance the preexisting stemness program and
potential. We, therefore, hypothesize that a subset of mature B cells is transiently endowed
with stem-like epigenetic features, which are hijacked by specific lymphoma drivers, and
constitute the molecular basis of their increased tumorigenic potential and tumor
repopulating capacity. To address this hypothesis, we have built an interdisciplinary team of
collaborators with expertise in stem cell reprogramming, epigenetics, immunobiology, single-cell
technologies and lymphoma research. We have devised an innovative and bold approach
employing multiple cutting-edge single-cell and chromatin technologies, as well as ex vivo and in
vivo functional assays that will allow us to (i) determine the key regulators that promote or prevent
increased GC B-cell plasticity in normal and cancerous contexts, (ii) decipher the signal and inter-
cellular dependencies that enable emergence of a GC stem-like state and key vulnerabilities and
(iii) dissect the synergies between common lymphoma drivers with GC stem-like properties,
contributing to aggressive disease and relapse. The discovery of B-cell stem-like features and
subpopulations will be paradigm-shifting and have a tremendous impact on the way we
understand and treat lymphomas, opening new avenues for the development of superior
diagnostic and therapeutic strategies.

## Key facts

- **NIH application ID:** 10873785
- **Project number:** 5R01CA283327-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Effie Apostolou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,699
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10873785

## Citation

> US National Institutes of Health, RePORTER application 10873785, Characterizing stem cell-like B cell subpopulations and dissecting their role in tumorigenesis (5R01CA283327-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10873785. Licensed CC0.

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