The surfaces and interiors of your cells contain proteins and other molecules called antigens. This unique combination of markers, known as an immunophenotype, acts like a cellular fingerprint that identifies a cell’s type and stage of development. When this fingerprint deviates from the normal, healthy pattern, it is called an aberrant immunophenotype. These alterations signal that something is amiss, providing an important clue for diagnosing and managing certain diseases.
Defining Aberrant Immunophenotypes
An aberrant immunophenotype is any pattern of antigen expression that differs from the normal process of cell development. This deviation suggests a disruption in the genetic programs that guide a cell’s life cycle. These abnormalities can manifest in several distinct ways.
- Lineage infidelity, where a cell expresses markers typically associated with a completely different cell type. For example, a developing white blood cell of the lymphoid lineage might wrongly express markers characteristic of the myeloid lineage.
- Overexpression of a normal marker, where a cell produces far more of a specific antigen than its healthy counterparts.
- Underexpression or complete absence of markers that should be present, which points to a failure in the cell’s normal production machinery.
- Asynchronous expression, where a cell simultaneously displays markers from different stages of its own development, such as showing both very early and late-stage antigens at the same time.
Techniques for Identifying Aberrant Cells
The primary technique for identifying cells with aberrant immunophenotypes is multiparameter flow cytometry. This technology allows for the rapid and precise analysis of millions of cells from a sample, such as blood or bone marrow. The process involves tagging specific antibodies with fluorescent dyes; each antibody is designed to bind to a particular marker on or inside a cell.
As prepared cells flow in a single file stream through a laser, the fluorescent tags are excited and emit light. Detectors within the instrument capture this light, measuring the intensity and color for each individual cell. This data allows scientists to build a detailed profile of which markers are present on each cell and in what quantity. By analyzing this information, they can distinguish abnormal cells from the surrounding healthy cell populations.
This method is sensitive enough to detect very small populations of aberrant cells, which is important for initial diagnosis and for monitoring disease after treatment. Another method is immunohistochemistry. This technique also uses antibodies to detect specific antigens but does so within a tissue sample, providing information about where the aberrant cells are located within the tissue structure.
Aberrant Immunophenotypes and Disease Link
The presence of an aberrant immunophenotype is strongly associated with cancers of the blood and bone marrow, known as hematologic malignancies. In these diseases, the antigenic fingerprint of the cancerous cells helps distinguish them from their normal counterparts. This abnormal expression is a direct consequence of the genetic mutations that drive the cancer, which disrupt normal gene expression and cell development.
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are two examples where aberrant immunophenotypes are a hallmark of the disease. In AML, it is common to see myeloid cancer cells expressing lymphoid-associated markers like CD7. Conversely, in B-cell ALL, the leukemic cells may aberrantly express myeloid antigens such as CD13 and CD33. These patterns of lineage infidelity are not random, as specific aberrancies can be linked to particular subtypes of leukemia.
For instance, the expression of the B-cell marker CD19 on AML cells is associated with a specific genetic abnormality known as the t(8;21) translocation. Different types of lymphomas also exhibit characteristic aberrant patterns that aid in their classification. Aberrant immunophenotypes can also be seen in non-malignant conditions or in pre-cancerous states like myelodysplastic syndromes (MDS), where the bone marrow does not produce enough healthy blood cells.
Clinical Use in Diagnosis and Monitoring
The identification of leukemia-associated immunophenotypes (LAIPs) is a component of clinical practice for hematologic cancers. Its first application is in diagnosis. By identifying the unique set of markers on malignant cells, clinicians can accurately classify the type of leukemia. This is important because different types, such as AML versus ALL, require different treatment strategies.
Beyond the initial diagnosis, specific aberrant patterns can provide prognostic information. The presence of certain markers may be associated with more aggressive forms of the disease or predict how a patient is likely to respond to standard therapies. For example, the aberrant expression of CD33 in B-ALL has been correlated with a poorer prognosis, which helps doctors tailor treatment plans.
A significant application is monitoring the response to treatment, specifically in the detection of Minimal Residual Disease (MRD). After chemotherapy, routine methods may not detect the very small number of cancer cells that can remain. Because these lingering cells retain their aberrant immunophenotype, flow cytometry can identify them at very low levels. Detecting MRD is a strong indicator that the cancer may relapse, allowing doctors to intervene with further treatment.