# The role of HIV Vif in clonal hematopoiesis and malignant transformation (HIV-Associated Cancers in Aging Populations)

> **NIH NIH P30** · BAYLOR COLLEGE OF MEDICINE · 2024 · $250,000

## Abstract

We accrue somatic mosaicism with age in many tissues. In the blood system, this is called clonal hematopoiesis
(CH). CH is a premalignant condition in which hematopoietic stem cells (HSCs) accrue 1-2 mutations among
~20 genes such as DNMT3A, TET2, and ASXL1. The CH clone size and the rate at which clones expand, which
are promoted by external factors such as inflammation, are strong predictors of malignant transformation of CH
into hematologic malignancies. Consistently, inflammation has been shown to promote the progression of CH to
hematologic malignancies. HIV-infected patients exhibit signatures of enhanced inflammation, such as activated
immune cells and cytokine expression, even when the patients are treated with antiretroviral therapies (ART).
Indeed, people living with HIV (PLWH) have higher incidence of CH, particularly those with ASXL1 mutations,
than HIV negative population. Notably, PLWH have a higher risk of developing hematologic malignancies such
as non-Hodgkin lymphoma (NHL) and myelodysplastic syndromes (MDS), suggesting an association between
the elevated CH prevalence among PLWH and its malignant transformation. The fact that PLWH treated with
ART have high incidence of CH raises a possibility that HIV infection promotes CH independently of viral load or
inflammation. HIV-infected human hematopoietic stem cells (HSCs) have been found in PLWH, further
supporting the possibility that HIV infection may alter HSC function cell intrinsically to confer competitive
advantages to mutant HSCs. The objective of this project is to elucidate the molecular mechanisms underpinning
the increased prevalence of CH and its transformation to malignancies among PLWH. In Aim 1, we will study
whether Asxl1 mutant HSCs expands upon HIV infection. In Aim 2, we will examine whether HIV infection
transforms Asxl1 mutant HSCs to myeloid neoplasms. Completion of this study will provide novel insights into
the effects of HIV infection on clonal expansion and subsequent transformation of Asxl1 mutant HSCs.

## Key facts

- **NIH application ID:** 11067438
- **Project number:** 3P30CA125123-18S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Daisuke Nakada
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $250,000
- **Award type:** 3
- **Project period:** 2007-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11067438

## Citation

> US National Institutes of Health, RePORTER application 11067438, The role of HIV Vif in clonal hematopoiesis and malignant transformation (HIV-Associated Cancers in Aging Populations) (3P30CA125123-18S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11067438. Licensed CC0.

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