Genetics

A t(14;18) translocation (Plate 10.2; Figure 10.4) is found in >85% of follicular lymphomas. This rearrangement puts the BCL-2 gene under the transcriptional control of elements from the immunoglobulin heavy chain locus. The BCL-2 protein functions to oppose programmed cell death. It is presumed that BCL-2 expression in malignancies such as follicular lymphoma permits survival of the cancer cells under conditions (cell cycle checkpoint violation, metastatic location, genomic instability) that would otherwise trigger programmed cell death. The cloning of BCL-2 led to the identification of a family of related proteins. While some are anti-apoptotic, like BCL-2, many are pro-apoptotic, but all function in the control of apoptosis.

Follicular lymphoma can transform into a higher-grade lymphoma with DLBL morphology. Numerous genetic changes have been associated with this transformation, including trisomy 7, loss of p53, and c-MYC rearrangements.

Lymphoplasmacytoid lymphoma is an indolent lymphoma. The cells of this lymphoma have a phenotype that lies midway between those of mature lymphocytes and plasma cells, for which reason they are often nicknamed 'plymphocytes'. This lymphoma commonly expresses IgM, which can lead to the syndrome of Waldenstrom's macroglobulinemia. Waldenstrom's macroglobulinemia is characterized by IgM ex

Chromosome 18 Chromosome 14

Chromosome 18 Chromosome 14

Fig. 10.4 Detection of t(14;18) by PCR amplification t (14 ; 18)

Fig. 10.4 Detection of t(14;18) by PCR amplification pression, hyperviscosity, bleeding, Raynaud's phenomenon, visual disturbances, and other neurological symptoms.

Roughly half of all lymphoplasmacytoid lymphoma cases will demonstrate the t(9;14), which juxtaposes the PAX-5 gene and the IgH locus. PAX-5 encodes the BSAP (B-cell specific activator protein), which is a transcription factor. Its expression is associated with increased expression of genes important in early B-cell development and decreased expression of the p53 tumor suppressor.

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