How to Determine if a Cell Is Myeloid or Lymphoid

The body’s blood and immune cells are divided into two major families: myeloid and lymphoid. Myeloid cells are the body’s first responders, forming the bulk of our innate immune defenses. Lymphoid cells are the specialists, creating a targeted and long-lasting adaptive immunity against specific invaders. Understanding a blood cell’s lineage is a foundational task in medicine, informing everything from routine blood analysis to the diagnosis of serious diseases.

The Foundation of Hematopoiesis

All blood cells originate from hematopoietic stem cells (HSCs) found primarily in the bone marrow. Through a process called hematopoiesis, these stem cells continuously divide to produce progenitor cells. This ensures a constant supply of new blood cells to replace old and expired ones.

The first split in this developmental path is the differentiation of the HSC into one of two specialized progenitors: the common myeloid progenitor (CMP) or the common lymphoid progenitor (CLP). This is the definitive point of divergence that establishes the division between the two main arms of the blood and immune systems. Once a cell commits to one of these paths, it cannot cross over to the other.

From these two progenitors, all specialized blood cells are formed. The common myeloid progenitor gives rise to a wide array of cells, including:

• Erythrocytes (red blood cells)
• Platelets (responsible for clotting)
• Neutrophils
• Basophils
• Eosinophils
• Monocytes

In contrast, the common lymphoid progenitor develops exclusively into lymphocytes, which include B-cells, T-cells, and natural killer (NK) cells, the primary actors in adaptive immunity.

Microscopic and Staining Identification

One of the most direct methods for distinguishing between myeloid and lymphoid cells is through visual examination under a light microscope. This technique relies on observing the cell’s morphology, or its physical characteristics like size, shape, and internal structures. To make these features visible, blood smears are treated with chemical dyes, most commonly the Wright-Giemsa stain.

After staining, myeloid cells, particularly in their granulocyte forms like neutrophils, are larger. A telling feature is a complex, multi-lobed nucleus and the presence of visible granules in their cytoplasm, which is the substance that fills the cell. These granules contain various enzymes and proteins related to their function in fighting off pathogens.

Lymphoid cells are smaller and have a more uniform appearance. The lymphocyte is characterized by a large, round, or slightly indented nucleus that takes up most of the cell’s volume. This leaves only a thin rim of cytoplasm, which appears as a pale blue halo around the dark purple-staining nucleus. Unlike their myeloid counterparts, the cytoplasm of lymphoid cells is agranular, meaning it lacks prominent granules.

These morphological clues are based on the mature forms of the cells. Identifying the lineage of very young or abnormal cells, known as blasts, can be more challenging as they often look very similar. While a trained eye might spot subtle differences, more advanced techniques are required to make a definitive determination.

Immunophenotyping with Cell Surface Markers

Modern cell identification uses a technique called immunophenotyping, which identifies cells based on the specific proteins, known as antigens, present on their surface. These proteins are cataloged using a “cluster of differentiation” (CD) system, where each unique marker is assigned a number. Different cell lineages express distinct combinations of these CD markers, creating a molecular fingerprint for each cell type.

The primary tool for detecting these markers is an instrument known as a flow cytometer. In this process, a sample of blood or bone marrow is mixed with antibodies that have been engineered to recognize specific CD markers and are tagged with fluorescent molecules. As the cells flow one by one through a laser beam inside the cytometer, the fluorescent tags light up, allowing the machine to count and sort the cells based on which markers they carry.

This technology allows for a highly precise way to determine a cell’s lineage. Myeloid line cells express markers such as:

• CD33
• CD13
• CD14 (identifies monocytes)
• Myeloperoxidase (MPO), an enzyme found inside myeloid cells

Conversely, lymphoid cells have their own unique set of identifiers. T-lymphocytes are characterized by the presence of the CD3 marker, B-lymphocytes are identified by their expression of CD19 and CD20, and Natural killer (NK) cells are recognized by the CD56 marker. By analyzing the complete pattern of these surface proteins, clinicians and researchers can definitively classify a cell population as myeloid or lymphoid.

Clinical Relevance in Disease Diagnosis

The ability to accurately distinguish between myeloid and lymphoid cell lines has profound implications in clinical medicine. A primary application is in the diagnosis and classification of acute leukemias, which are aggressive cancers of the blood-forming tissues. These diseases are defined by the rapid proliferation of immature, cancerous blood cells, and the specific lineage of these cells determines the type of leukemia.

When the cancer arises from the myeloid line, the disease is called Acute Myeloid Leukemia (AML). If the cancer originates from the lymphoid line, it is known as Acute Lymphoblastic Leukemia (ALL). This distinction is important because the treatment protocols for each are entirely different and highly specific to the cell lineage involved.

A patient diagnosed with ALL will receive a chemotherapy regimen designed to target and destroy cancerous lymphoblasts, which would be ineffective against myeloid cancer cells. Similarly, the therapies used to treat AML are tailored to the biology of myeloid blasts and would not work for ALL. An incorrect classification could lead to administering the wrong treatment, with serious consequences for the patient’s outcome.

Therefore, the techniques of microscopy, staining, and immunophenotyping are used together to provide a definitive diagnosis. This precise classification allows oncologists to select the appropriate therapeutic strategy, predict the likely course of the disease, and give the patient the best possible chance for remission and recovery.