Not every day does an investigator, while still a medical student, stumble upon an under-researched facet of medicine and identify what could turn out to be her life’s work. But that’s what happened when Hematologist Lauren Merz, MD, MSc, now an assistant professor at Rogel Cancer Center at the University of Michigan in Ann Arbor, Michigan, first learned about “benign ethnic neutropenia.”

Back in the day, Merz was a medical student at Michigan, writing a case report about a child with this diagnosis.

“I tried to come to terms with the fact that this kid missed an entire soccer season due to a ‘disease’ that isn’t a disease,” she said. “‘Benign ethnic neutropenia’ and similar terminology served a historical purpose when the link between Duffy status and circulating neutrophils was not established, but this terminology is now outdated and considered pejorative.”

That case report patient was one of an estimated two out of three people who identify as Black or African American individuals whose red blood cells lack the Duffy antigen. Caused by a mutation in the ACKR1 gene, this mutation offers some protection against malaria infection. Fewer than 1% of people of European or Asian ancestry have this Duffy null phenotype, Merz said.

The Duffy null phenotype is associated with lower absolute neutrophil counts (ANCs) but, Merz, the senior author, on a recent review reported that these readings are not linked to increased infection risk. “In fact, we see about 25% of patients with the Duffy null phenotype will have a neutrophil count below 2000, which is what many of our institutions will set as the lower limit of normal for neutrophils,” she said.

This matters because there is a wide range of health inequities associated with the Duffy null phenotype, such as inappropriate investigations including bone marrow biopsies, inability to enroll in clinical trials, and lack of access to other critical treatments or medications, Merz said.

For example, eligibility criteria for clinical trials may inadvertently exclude participation due to ANC thresholds within the expected Duffy null ANC reference interval. These criteria can contribute to the underrepresentation of people from African and Middle Eastern ancestry and limit how generalizable the trial results are. And the Common Terminology Criteria for Adverse Events, widely used across clinical trials, defines “low neutrophil counts” within the Duffy null expected interval as a grade 1 or grade 2 criteria, Merz and her co-authors wrote.

Even as a relatively new investigator, Merz has made an impact on the field. In 2023, she published the first Duffy null-specific ANC reference range. The American Society of Hematology (ASH) has recognized her efforts, too, updating the terminology around this variant to Duffy null-associated neutrophil counts and publishing a variety of related educational resources for clinicians.

Merz is also the principal investigator on a grant through the Doris Duke Foundation and the ASH to accelerate the update of Duffy null reference ranges across the country. The team expects to publish their results from 23 leading institutions in 2026. In the meantime, Merz said, ASH is preparing to release a new guideline that strongly recommends obtaining Duffy status testing of participants in all clinical trials.

Merz fully expects her work on the Duffy null phenotype to occupy her for the foreseeable future. “There is a lifetime of work to do. I joke that I’m trying to put myself out of a job because I’d love to never again see a Duffy null patient in clinic,” she said. “I want that to be normal and well-described at a primary care clinic due to universal Duffy screening.”

Merz recently sat down with Medscape Medical News. The following interview has been edited for clarity.

As a hematologist, it makes sense that much of your work to date on Duffy status has focused on blood cancers. How does Duffy status affect patients with other diseases?

It’s so clear that patients experience harm in the blood cancer space due to the invasiveness of our testing, but it applies to many other cancers, too. For example, patients with breast cancer who are Black individuals are much more likely to experience dose reductions and treatment interruptions. We also have good data on the effects of prescribing guidelines on hydroxyurea in sickle cell disease, azathioprine in rheumatological disease, and clozapine in schizophrenia.

What drew you to Duffy antigen status as an area of clinical research?

It was the experience of seeing patients in clinic who had spent 3-6 months worrying after being told their ANC was too low and googling things like leukemia and aplastic anemia. They’re simultaneously relieved when I tell them they’re fine and devastated they had to be in a state of anxiety for months. I’m glad to give them good news, but how do I give them back those months of anxiety?

The roots of my interest go further back into childhood, when I realized that medicine is a beautiful overlap of social justice and science. My father still practices family medicine and has always worked at migrant clinics or federally qualified healthcare centers. That’s what I originally thought I was going to do, but I found I can affect even more people through my research than what I could realistically do person-to-person in the clinic.

What has this work taught you about laboratory reference ranges?

Even as a physician, I had no idea that each major institution essentially establishes its own reference range for every major test based on manufacturer recommendations and variations in their community. But those samples from people who are representative of the community often end up being more of a convenience sample than truly representative. It only takes 120 samples to establish a new reference range and if an institution wants to “borrow” the range of a neighboring institution, they only need to have 18 of 20 samples be within that range to adopt it.

Laboratory medicine specialists know that reference ranges are supposed to be a suggestion or a guideline but that’s not how we in clinical medicine have been trained, and that’s not the way that patients look at them, either. Collectively, we are probably missing multiple subpopulations in our reference ranges. Even when we do end up including a few Black or African American people in our reference range samples, that might not be enough to create a truly representative reference interval. We now know that Duffy null is a subpopulation that deserves its own reference interval.

What should physicians do when a patient who is likely to be Duffy null presents with a low ANC?

If someone has a neutrophil count that’s slightly lower than what the reference interval says is normal — especially if they are Black or African American individuals — we are obligated as clinicians to look at that patient critically and ask ourselves if they are pathologically neutropenic. But with the overload that we all feel in the healthcare system, there often isn’t that time or space to be able to think critically like that. That’s when we often lean on reference ranges as being really concrete, which can do a disservice to our patients.

Merz disclosed consulting for Johnson & Johnson and 23andMe.

Darcy Lewis writes about clinical medicine from Chicago.