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Cluster of Differentiation

20 Mar

Table 1 Cluster of differentiation was proposed as a system to classify monoclonal antibodies. The antibodies, their cluster of differentiation and their linage is listed in the table above

The technique for production of monoclonal antibodies invented by Cesar Milstein and Georges J. F. Köhler in 1975 allowed production of antibodies that could identify an array of antigens on leucocyte surfaces. The monoclonal antibodies gave insights into the process of maturation of leucocytes allowing recognition of stages of differentiation that were not evident by morphology-based methods. Immunophenotyping, the classification cells according to antigens they express, has highlighted the inhomogeneity of morphological subtypes of leukaemia and lymphomas. This has allowed recognition of new disease entities and development of specific management protocols for some of these. Today the impact of immunophenotyping is seen across oncopathology. Few diagnoses are made without the use of immunophenotyping. The period few years after the development of the first anti-leucocyte monoclonals was a period of confusion. In a reflection of the ease of mastering the hybridoma technology, the number of monoclonal antibodies proliferated resulting in chaos about the identity of antigen they characterized (table 1). The CD4 antigen was recognized by the OKT4 (Ortho Diagnostics) and the Leu-3 (Becton Dickson) monoclonal antibodies. It was known as the Leu 3 and T4 antigen. The cluster of differentiation nomenclature was proposed at the 1st International Workshop and Conference on Human Leukocyte Differentiation Antigens at Paris in 1982 as a system of classification of monoclonal antibodies directed against leucocyte surface antigens. Following adoption of the cluster of differentiation nomenclature OKT4 and Leu3 would be called anti-CD4 antibodies, as would any new antibody directed against the same antigen. The antigen defined by these is referred to as CD4. Over 200 antigens are now recognized. Table 2 gives the lineage specificity of some markers. Some CD antigens are designated with suffix ‘w’, e.g. CDw12. These are antigens that have been identified by only one antibody or by up to two antibodies generated in the same lab (Bull. WHO 1994; 72:807-808).

Table 2 Some commonly used lineage specific markers</h5.

The complete list of CD antigens is available at the Human Cell Differentiation Molecules (HCDM) site.

Auer Rods

10 Jun 061011_1434_AuerRods1.jpg

Auer rods are needle shaped azurophilic intracytoplasmic inclusion bodies described by John Auer in 1906. They are 0.1-2μ wide and 3-6μ long and are formed by fusion of lysosomes. They contain peroxidase and lysosomal enzymes. They are seen in acute leukaemia (myeloblastic, promyelocytic, monomyelocytic and monocytic), myelodysplastic syndromes (RAEB-2) and chronic monomyeloid leukemia. Myelodysplastic syndromes, according to the WHO classification are disorders cytopenias and <20% blasts in the bone marrow. Patients with 10-19% blasts are classified as RAEB–2. Documenting Auer rods is important in examination of bone marrow smears of patients suspected to have MDS as a patient is classified as RAEB-2 even with <10% blast if Auer rods are present. Of the Romanovsky stains there are reports of Leishman’s stain being suboptimal for staining for Auer rods. The prognosis of patients with myelodysplastic syndromes worsens with increasing blasts. Patients with Auer rods have a worse prognosis than similar patients without Auer rods (Am J Clin Pathol 124:191; 2005). A lymphoid leukaemia can be excluded in patients with Auer rods.

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