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Flow cytometric characterization of acute myeloid leukemia. Part II. Phenotypic heterogeneity at diagnosis
L W Terstappen1, M Safford, S Könemann
1Becton Dickinson Immunocytometry Systems, San Jose, CA 95131.
Insights
Multidimensional flow cytometry reveals unique aberrant antigen expression patterns in acute myeloid leukemia (AML) bone marrow cells. This distinct profiling aids in differentiating leukemic cells from normal cells, crucial for monitoring treatment response.
Area of Science:
- Immunology
- Hematology
- Oncology
Context:
- Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
- Accurate characterization of leukemic cells is essential for diagnosis and treatment monitoring.
- Multidimensional flow cytometry offers high-resolution analysis of cellular antigens.
Purpose:
- To analyze aberrant antigen expression patterns on bone marrow aspirates from newly diagnosed AML patients.
- To identify unique antigenic profiles of leukemic cells using multidimensional flow cytometry.
- To compare antigen expression in AML with normal bone marrow to define aberrant patterns.
Summary:
- Eighty AML patients' bone marrow aspirates were analyzed for antigen expression (CD2-38, HLA-DR) and light scatter profiles.
- Aberrant expression patterns included non-myeloid antigen presence, asynchronous/over/under-expression of myeloid antigens, and heterogeneous/homogeneous expression.
- Each AML patient exhibited a unique antigenic profile, distinguishable from normal cells by aberrant expression and light scatter characteristics.
Impact:
- Establishes that multidimensional flow cytometry can define unique antigenic signatures for individual AML patients.
- Enables discrimination between leukemic and normal cells, facilitating the detection of minimal residual disease (MRD).
- Provides a foundation for improved diagnostic strategies and personalized therapeutic monitoring in AML.
Abstract:
The frequency and distribution of aberrant antigen expression are analyzed on bone marrow aspirates from 80 patients with newly diagnosed acute myeloid leukemia (AML) by multidimensional flow cytometry. Parameters examined are the light scatter profile of the leukemic cells and the correlative expression of different combinations of the CD2, 4, 5, 7, 11b, 11c, 13, 14, 15, 16, 33, 34, 38, and HLA-DR antigens. Antigen expression on leukemic cells in bone marrow is described by characteristic antigen expression patterns describing: (i) the percentage of cells expressing the antigen; (ii) the antigen density; and (iii) the distribution of the antigen on the leukemic cells. Typically the non-myeloid antigens are homogeneously expressed by the leukemic cells, whereas the myeloid associated antigen CD11b, CD11c, CD14, and CD15 are heterogeneously expressed. Comparison of the antigenic profiles of 80 bone marrow aspirates revealed an extreme interclonal heterogeneity. Comparison of the antigen expression patterns found in AML patients with the antigen expression in normal bone marrow revealed four patterns of aberrant antigen expression in AML: (i) expression of nonmyeloid antigens (i.e. CD2, CD5, and CD7 were present in 57, 60, and 37% of the patients, respectively); (ii) asynchronous expression of myeloid associated antigens (i.e. co-expression of CD34 and CD15 in 25% of the patients and expression of CD16 on immature myeloid cells in 15% of the cases); (iii) over-expression of myeloid associated antigens (e.g. CD34 in 16% of the cases and CD14 on neutrophilic cells in 19% of all patients); and (iv) absence of expression of myeloid associated antigens (e.g. lack of CD33 in 21% of the cases and lack of both CD11b and CD15 in 6% of all patients. Multidimensional flow cytometric analysis of bone marrow aspirates of AML patients disclosed that the leukemic cells of each AML patient had a unique antigenic profile and could be discriminated from their normal counterparts based on aberrant antigen expression and typical light scatter profiles. The ability to distinguish leukemic cells from normal cells allows the detection of residual leukemic cells during and after chemotherapy.