# Role and Mechanisms of VAV1 alterations in Peripheral T-cell Lymphomas

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $363,164

## Abstract

Project Summary/Abstract
Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous and poorly understood
pathological group of non-Hodgkin lymphomas associated with poor prognosis. Despite major
progress in recent years in the identification of genomic drivers in PTCL, understanding their
mechanisms of transformation and identifying therapeutic targets remain a high priority in the
field. Recently we have identified novel genetic alterations in the VAV1 oncogene in PTCL using
a combination of RNAseq analysis and targeted sequencing of candidate genes. Most VAV1
genomic alterations are fusions and small intragenic deletions affecting the C-terminal domain of
the protein. Our central hypothesis is that the VAV1 alterations lead to increase activation of
signaling pathways downstream of VAV1 and act as oncogenic drivers of PTCL. Our preliminary
results demonstrate that expression of the recurrent Vav1-myo1f fusion induces lymphomas that
recapitulate the histology and molecular pathology of high-risk PTCL. The goals of this project are
to characterize the mechanisms by which VAV1-MYO1F fusion promotes lymphomagenesis in
vivo and to explore emerging specific therapeutic vulnerabilities in PTCL preclinical models.

## Key facts

- **NIH application ID:** 10438898
- **Project number:** 5R01CA256341-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Teresa Palomero
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $363,164
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438898

## Citation

> US National Institutes of Health, RePORTER application 10438898, Role and Mechanisms of VAV1 alterations in Peripheral T-cell Lymphomas (5R01CA256341-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438898. Licensed CC0.

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