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Genotyping May Help Avoid Unnecessary Bone Marrow Biopsies in African Americans

NEW YORK – Bone marrow biopsies may be used unnecessarily in some African American individuals who are genetically predisposed to having relatively low white blood cell counts, according to a retrospective genetic analysis by researchers at Vanderbilt University Medical Center and elsewhere.

The study found that white blood cell counts may be low due to a rs2814778-CC variant in the promoter of the atypical chemokine receptor 1-coding gene ACKR1. While this variant is relatively uncommon in individuals of European ancestry, it appears to be found in more than 60 percent of African Americans and is found at especially high frequency in some populations from sub-Saharan Africa.

Results of the study, published in JAMA Internal Medicine on Monday, highlight the limitations of trying to extrapolate "normal" blood cell counts based on a limited number of populations, senior author Jonathan Mosley, a clinical pharmacology researcher at Vanderbilt University Medical Center, explained in an email.

"[R]eference ranges for white blood cell (WBC) counts or neutrophil counts are not appropriately calibrated to large population groups, including many African Americans," Mosley said, noting that "inappropriate reference ranges lead to unnecessary health care utilization in the form of excessive testing." 

For their study, he and his colleagues looked back at array-based genotyping data for 399 African American individuals who had bone marrow biopsies at one of three medical centers in the US over more than two decades, from early 1998 to the end of 2020. Their results indicated that the rs2814778-CC genotype — previously linked to low white blood cell counts — was present in some 67 percent of the individuals who were referred for bone marrow biopsies based on their medical history, beyond low white blood cell counts alone.

In contrast, the team noted that the rs2814778-CC genotype turned up in all but one of the 35 patients who underwent bone marrow biopsies solely based on lower-than-usual white blood cell counts. Those results hinted that testing may have been unnecessary in this small subset of patients, particularly since 97 percent of them had normal biopsy results, compared to 55 percent in the subset of 243 African American patients who did not carry the rs2814778-CC genotype.

"The genotype that causes lower white blood cells was almost always present in African American individuals who had a bone marrow biopsy solely for a low white blood cell count," first author Sara Van Driest, a researcher at Vanderbilt, said in a statement. "We hope that in the future, we can do a better job of recognizing these individuals with a benign cause for their low white blood cells counts so that bone marrow biopsies can be avoided."

The study also points to the need for coming up with broader white blood cell reference ranges that take the rs2814778-CC variant into account to avoid pathologizing blood cell counts that fall into the typical range for individuals carrying this genotype, Mosley said, noting that the variant is not currently genotyped as a routine part of clinical care in this setting.

"We've essentially created this racial health disparity by not fully considering how genetic variation affects white blood cell levels," he said in a statement. "Our study supports genotyping African Americans before performing a bone marrow biopsy for the indication of isolated low white blood cell counts."