CD33 expression on natural killer cells is a potential confounder for residual disease detection in acute myeloid
Ashley M Eckel1, Sindhu Cherian1, Valerie Miller1
1Department of Laboratory Medicine, University of Washington, Seattle, Washington.
Abstract:
Detection of minimal/measurable residual disease (MRD) in acute myeloid leukemia (AML) is important for guiding patient-specific clinical management. Natural killer (NK) cells can express various markers not typically associated with NK lineage, potentially confounding the detection of MRD by flow cytometry. We have observed CD33 expression on NK cells when evaluating for AML MRD in routine clinical practice in multiple patient samples. To characterize CD33 expression on NK cells, 40 peripheral blood or bone marrow samples with NK cells present at >5% of lymphocytes were selected for further assessment of NK cell phenotype and CD33 expression. Seven of the 40 samples (17.5%) were found to have CD33 expression on at least 5% of the NK cells. The CD33-positive NK cell population accounted for an average of 11.4% of NK cells (median 11.9%, range 8.0-15.3%) and 2.2% of total white cells (median 1.1%, range 0.1-10.1%). This NK cell subset expressed bright CD2, bright CD56, and dim CD16. On average, CD33 expression on NK cells was dimmer than on monocytes (mean median fluorescence intensity ratio 0.4; range 0.1-1.0). This study characterizes expression of CD33 on NK cells. Recognition of this pattern of antigen expression is critical in evaluating samples for MRD in patients with myeloid neoplasms, particularly AML.
Insights
CD33 expression on natural killer (NK) cells can interfere with minimal residual disease (MRD) detection in acute myeloid leukemia (AML). This study characterizes this NK cell subset, crucial for accurate AML MRD assessment.
Area of Science:
- Hematology
- Immunology
- Flow Cytometry
Background:
- Accurate detection of minimal/measurable residual disease (MRD) is vital for managing acute myeloid leukemia (AML).
- Non-specific antigen expression on immune cells, such as natural killer (NK) cells, can complicate MRD assessment by flow cytometry.
- CD33 is a marker typically associated with myeloid lineage, including AML blasts.
Purpose of the Study:
- To investigate and characterize the expression of CD33 on NK cells.
- To determine the frequency and phenotype of CD33-expressing NK cells in patient samples.
- To highlight the clinical relevance of recognizing this phenomenon for accurate AML MRD evaluation.
Main Methods:
- Analysis of 40 peripheral blood or bone marrow samples with >5% NK cells.
- Flow cytometry was used to assess NK cell phenotype and CD33 expression.
- Comparison of CD33 expression intensity between NK cells and monocytes.
Main Results:
- CD33 expression was detected on NK cells in 17.5% of analyzed samples.
- The CD33-positive NK cell population represented a significant fraction of NK cells and total white blood cells.
- These NK cells exhibited a distinct phenotype (CD2 bright, CD56 bright, CD16 dim) and dimmer CD33 expression compared to monocytes.
Conclusions:
- CD33 can be aberrantly expressed on a subset of NK cells.
- This finding is critical for accurate interpretation of flow cytometry data in AML MRD detection.
- Awareness of CD33+ NK cells is essential to avoid misclassification of leukemia cells and ensure proper patient management.
