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Gene Rearrangement for B and T cells

Lymphocytes recognize and respond to foreign antigens by means of specific membrane receptors. B cells have surface immunoglobulin receptors and T cells have T-cell receptors. The human genome does not contain enough unique DNA sequences to code for the vast repertoire of receptors needed to recognize all of the foreign antigens a person is exposed to during their lifetime. To overcome this limitation, the immunoglobulin and T-cell receptor genes, unlike most other genes, undergo a complex series of DNA rearrangements to produce more than one billion unique receptors.

DNA from a polyclonal population of lymphocytes contains multiple rearrangements of a given gene, each with a different enzyme restriction site. None of these rearrangements is sufficiently prevalent to be detectable. However, when a neoplastic population of lymphocytes is present, clonal expansion of a single lymphocyte's gene rearrangement results in detectable bands. Gene rearrangement studies can help to distinguish benign from malignant lymphocytosis.

When a diagnosis of lymphoma or lymphoid leukemia is already established, gene rearrangement analysis can readily determine whether the neoplasm is of T or B cell lineage. Rearrangement of immunoglobulin genes (heavy chains and kappa and lambda light chains) is largely restricted to B cells, while rearrangement of T-cell receptor genes is restricted to T cells. A few discrepancies have been noted, especially in acute leukemias. Gene rearrangements occur earlier in B and T cell differentiation than the development of cell surface B and T cell antigens. Therefore, gene rearrangement analysis can determine cell lineage at an earlier stage of differentiation than flow cytometry.

Gene rearrangement analysis of B cell lymphoid neoplasms also provides information about cell maturity. Most primitive B cell neoplasms have rearranged heavy chain immunoglobulin genes and normal light chain genes, whereas more mature types have rearranged heavy and light chain genes

Gene rearrangement analysis can be used to monitor recurrences of previously treated lymphoma or leukemia. It is extremely sensitive and can detect lymphocyte clones that comprise only 1% to 3% of the total cell population. Gene rearrangement analysis can also be used for staging, since it can detect occult cancers in tissue samples.

Reference value is no gene rearrangement detected.

Specimen requirements are:

Two 5 mL lavender top (EDTA) tubes of blood transported at room temperature,

One 5 mL lavender top (EDTA) tube of bone marrow transported at room temperature,

50 mL of body fluid shipped at room temperature,

A 5 X 5 X 5 mm piece of tissue trimmed of fat and connective tissue.

Fresh tissue must be processed immediately and shipped on dry ice.

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