# Evaluating the clinical implications for ACKR1/DARC associated neutropenia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $686,997

## Abstract

Abstract:
White blood cell (WBC) counts and neutrophil counts are among the most commonly used medical tests. WBC
counts and absolute neutrophil counts (ANC) are monitored closely in the setting of myelosuppressive therapy,
and neutropenia is often the dose limiting toxicity when dosing chemotherapy. An elevated WBC count is also
used in helping to diagnose and infection and risk stratifying patients with acute bacterial infections. Therefore,
accurate interpretation of the WBC and neutrophil count is crucial in many branches of medicine. WBC and
neutrophil counts vary substantially by race and ethnicity. African Americans, Latinos with African ancestry and
some Middle Eastern populations have lower WBC and lower ANC. We have previously mapped the genetic
variant underlying this difference. The variant maps to the promoter region of the Duffy Antigen Receptor
Chemokine (DARC/ACKR1) locus and results in lack of expression of the DARC antigen on the surface of red
blood cells. The allele which leads to loss of expression (Fya-/b- or Fy-) is the predominant allele in West Africa,
but rare outside of Africa and the Middle East. Individuals with Fy-/- genotype have WBC and ANC that is > 1
standard deviation lower than individuals with the other genotype. Despite over a decade of knowledge about
this effect, there has been little progress on incorporating this into clinical care. As a result, patients with this
genotype who are predominantly African American in the U.S. may receive lower doses of myelosuppressive
therapies and may be more likely to have reduced relative dose intensity of chemotherapy which may lead to
disparities in outcomes. Since WBC and ANC are used to diagnose and make prognostic inferences among
patients with infection, their care in the setting of severe infections may suffer. Therefore, large studies with
outcomes are needed to help guide clinicians on how to treat these patients. We propose to leverage large
biobanks tied to electronic health records to determine outcomes of patients on myelosuppressive therapies with
this genotype and to determine how to use WBC and ANC in the setting of infection. (1) We will examine
outcomes of patients on chronic myelosuppressive therapies by genotype. We will determine whether Fy-/-
genotype is associated with high incidence of neutropenia on myelosuppressive therapies and whether this leads
to dose reductions. We will examine the risk of infectious complications among patients with Fy-/- on
myelosuppressive therapies. (2) We will examine outcomes of patients on chemotherapy according to genotype.
We will determine if genotype is associated with relative dose intensity of chemotherapy and whether this is
associated with differences in overall survival among these patients. We will determine if infectious complications
are associated with genotype among patients on chemotherapy. (3) We will examine how WBC and neutrophil
to lymphocyte count ratios vary in the setting of acute infections and...

## Key facts

- **NIH application ID:** 10902009
- **Project number:** 5R01HL170627-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elad Ziv
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $686,997
- **Award type:** 5
- **Project period:** 2023-08-15 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902009

## Citation

> US National Institutes of Health, RePORTER application 10902009, Evaluating the clinical implications for ACKR1/DARC associated neutropenia (5R01HL170627-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10902009. Licensed CC0.

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