A recent study published in Clinical Cytometry has confirmed that CD123 is expressed on the surface of neoplastic mast cells in the vast majority of patients with systemic mastocytosis (SM), suggesting it may have potential as a therapeutic target.
In SM, abnormal mast cells grow uncontrollably and often display specific surface markers, such as CD25 and CD2. Researchers are now focusing on another marker called CD123, a protein that serves as a therapeutic target for drugs already used in treating other blood cancers.
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Researchers analyzed 142 bone marrow samples from 79 patients across various SM subtypes and 25 healthy controls, providing new data on the frequency of this marker in SM.
The study identified an overall CD123 positivity rate of 91% among SM cases, a finding that remained consistent across nearly all subtypes. Specifically, the marker was detected in 92% of patients with indolent SM (ISM), 94% of those with SM with an associated hematologic neoplasm (SM-AHN) and 100% of those with smoldering SM (SSM). In cases of mast cell leukemia (MCL), the positivity rate was 50%. These results are notably higher than those previously reported using other methods, which the authors attribute to the greater sensitivity of this particular analysis for detecting cell-surface proteins.
Interestingly, the research found that CD123 expression does not correlate with other common clinical indicators of the disease. There was no established link between the presence of CD123 and serum tryptase levels, KIT D816V mutation burden or the overall mast cell burden in the bone marrow.
While CD123 is already utilized as a therapeutic target in other blood-related malignancies, such as acute leukemias, its role in SM has been less defined. Beyond targeting mast cells directly, the researchers noted a potential dual benefit to targeting CD123: it may also affect certain immune cells (plasmacytoid dendritic cells) that frequently cluster alongside abnormal mast cells.
“These findings provide theoretical support for further work investigating the utility of CD123 as a therapeutic target in SM,” the authors noted.
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