Types of leukemia

Leukemia is a type of blood cancer that usually originates in bone marrow. Although it is the most common type of cancer in children, most cases of leukemia develop in adulthood. The common characteristic of leukemia is a high number of aberrant cells present in the blood. These cells are partially differentiated precursor blood cells with altered gene expression and the presence of specific plasma membrane markers. Leukemia is classified based on the type of aberrant cells found in patients. They can originate from lymphoid (lymphocytic leukemia) or myeloid (myeloid or myelogenous leukemia) lineage. Leukemia is then further divided into acute and chronic, depending on the disease progression. Investigating markers of the aberrant cells is indispensable for correct diagnosis and subclassification (immunofluorescence, immunohistochemistry, and flow cytometry), monitoring the disease progression, and the further development of therapeutic treatments.

Lymphocytic leukemia

The two main types of lymphocytic leukemia are chronic lymphocytic (CLL) and acute lymphocytic (ALL). Patients have elevated levels of lymphoblasts (precursors of white cells) in their blood. These can be either T or B cell lineage. CD3 (Figure 1), CD4, and CD8, as classic markers of T cells, are a good prognostic marker of patient survival (PMID: 20846097). CD19 (Figure 2), an antigen widely present on B cells, persists in its expression on B cell-related cancer cells. It is often used in diagnosis (PMID: 8528044). Additional markers, namely CD20 (Figure 3), CD22, CD24, and CD79a, are used to study minimal residual disease – drug-resistant leukemic cells (PMID: 9492773). Plasma membrane staining of CD38 (Figure 4) and CD49d is often used in the clinic and their expression correlates with the disease severity and its response to chemotherapy (PMID: 10477712). ZAP70, an intracellular protein, is also a predictor of leukemia. It is involved in promoting prolonged signaling of the BCR pathway and the survival of cancer cells (PMID: 18577710).

Figure 1. Immunohistochemical analysis of paraffin-embedded human lung cancer tissue slide using 17617-1-AP (CD3 antibody) at dilution of 1:1000 (under 40x lens) heat mediated antigen retrieved with Tris-EDTA buffer(pH9).

Figure 2. Immunohistochemical analysis of paraffin-embedded human tonsillitis tissue slide using 27949-1-AP (CD19 antibody) at dilution of 1:200 (under 10x lens) heat mediated antigen retrieved with Tris-EDTA buffer(pH9).

Figure 3. Immunohistochemical analysis of paraffin-embedded human appendicitis tissue slide using 60271-1-Ig (CD20 antibody) at dilution of 1:12800 (under 10x lens) heat mediated antigen retrieved with Tris-EDTA buffer(pH9).

Figure 4. Immunohistochemical analysis of paraffin-embedded human tonsillitis tissue slide using 25284-1-AP (CD38 Antibody) at dilution of 1:50 (under 10x lens)

Myeloid leukemia

There are two main types of myeloid leukemia: chronic myeloid (CML) and acute myeloid (AML). Patients display a higher level of myeloid cells (precursors of blood cells originating in the bone marrow: granulocytes, monocytes, erythrocytes, or platelets) in their blood. Typical markers of myeloid lineage cells can be used. For example, CD13 is expressed on monocytes and granulocytes, while CD11b is expressed at low levels by natural killer cells and expressed at high levels by monocytes, neutrophils, and eosinophils. AML is recognized by the accumulation of MPO-positive cells or cells positive for at least two antigens: nonspecific esterase, CD11c (Figure 5), CD14, CD64, lysozyme (PMID: 27069254). A specific cell subset, known as leukemic stem cells (LSCs), are cancer stem cells present in AML patients. They are characterized as CD34-positive and CD38-negative (PMID: 28357569).

Figure 5. Immunohistochemical analysis of paraffin-embedded human spleen tissue slide using 17342-1-AP (CD11c/Integrin alpha X Antibody) at dilution of 1:200 (under 40x lens).

Antibody-based techniques are indispensable in research, diagnosis, and for monitoring the treatment efficacy of leukemia. This is possible due to the use of protein markers, which are proteins present only on a specific subset of cells, thus allowing their identification.

Table 1 Markers used in research, diagnosis, and monitoring the progression of leukemia.