Diffuse Large BCell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, and this category of the WHO classification represents another heterogeneous group of BCLs. The most common chromosomal abnormalities identified thus far in DLBCL are BCL6 (3q27) abnormalities,24,25 t(14;18)(q32;q21) IGH/BCL2 translocations,26 and REL (2p12-16) amplifications, but routine diagnostic testing of DLBCL usually is not performed for these chromosomal abnormalities. IGH/BCL2 translocations occur in approximately 20% to 30% of DLBCL and are identical to those occurring in FL. The clinical significance of the IGH/BCL2 translocations in DLBCL is not clear. BCL6 translocations occur in about 40% of DLBCL, with numerous translocation partners. It is likely that the particular translocation partner dictates the prognostic significance of the BCL6 translocation; those involving the IGH locus appear to portend a more favorable prognosis than other partner genes. Pathologic mutations of BCL6 also occur in about 10% of DLBCL and may contribute to lymphomagenesis. Clinical testing usually is not done for BCL6 at diagnosis because of the lack of confirmed prognostic significance. If done, Southern blotting is usually the method of choice.

A promising new method of identification of prognostic subgroups of DLBCL is microarray gene expression profiling (GEP).27-29 By this method, a germinal center B-cell-like DLBCL subgroup (GCB) with a favorable prognosis and activated B-cell-like and unclassified DLBCL subgroups with a poorer prognosis have been identified. The GCB subtype of DLBCL expresses genes typical of normal germinal center B cells; REL amplification and t(14;18) translocations are specific to this subgroup. DLBCL is the most likely category of BCL in which miniar-rays first will be used for detection of patterns of GEP at the time of initial diagnosis to stratify patients for different treatment protocols.

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