New research suggests that clonality may underlie the cytopenias observed in patients with idiopathic cytopenias of undetermined significance (ICUS).
So researchers say these patients should be classified as having clonal cytopenias of undetermined significance (CCUS).
The team believes that recognition of CCUS as a clinical entity would help identify it as a formally defined diagnostic group and could aid future studies.
“We don’t know to what extent patients who have low blood counts and mutations are at increased risk of developing an overt malignancy,” said Rafael Bejar, MD, PhD, of the UCSD Moores Cancer Center in La Jolla, California.
“We hope that by defining CCUS, future studies will follow these patients to learn what these mutations mean for their future, as their genetically abnormal cells may represent early stages of subsequent blood cancers.”
Dr Bejar and his colleagues defined CCUS in Blood. Their research was funded, in part, by Genoptix Medical Laboratory, and several study authors are employees of Genoptix.
The researchers prospectively examined bone marrow samples from 144 patients with unexplained cytopenias. Seventeen percent of these patients were diagnosed with myelodysplastic syndromes (MDS), 15% with ICUS and some evidence of dysplasia, and 69% with ICUS and no dysplasia.
The team then sequenced patient samples looking for mutations in 22 frequently mutated myeloid malignancy genes. They identified somatic mutations in 71% of MDS patients, 62% of patients with ICUS and some dysplasia, and 20% of ICUS patients with no dysplasia.
Overall, 35% of ICUS patients carried a somatic mutation or chromosomal abnormality indicative of clonal hematopoiesis.
To build upon these findings, the researchers performed a retrospective analysis of data from 91 patients with lower-risk MDS and 249 patients with ICUS.
The team identified mutations in 79% of patients with MDS, 45% of patients with ICUS and dysplasia, and 17% of patients with ICUS and no dysplasia.
The researchers said the spectrum of mutated genes was similar among the 3 groups. The exception was SF3B1, which was rarely mutated in patients without dysplasia.
The team added that variant allele fractions were comparable between clonal ICUS (CCUS) and MDS, and the same was true for the patients’ mean age and blood counts. But CCUS was a more frequent diagnosis than MDS.
Dr Bejar and his colleagues said larger, carefully controlled studies will be needed to confirm the findings of this research.
