Ig Translocations In

Although IG translocations are rare in CLL34 and probably comprise no more than 5% of cases, they have allowed the identification of a number of genes of interest. They appear to be associated with aggressive disease. The presence of a t(11;14)(q13;q32) in a mature B-cell malignancy precludes the diagnosis of CLL; MCL in leukemic phase, a specific subtype of MCL, is most likely. Detection of IGH translocations is now performed by interphase FISH, but these methods have not been used to detect IG light chain translocations in any large series of CLL patients.

BCL2: All cases of CLL express high levels of BCL2 RNA and protein. It has been suggested that this highlevel expression is due to hypomethylation of the BCL2 promoter. Chromosomal translocations involving BCL2 are rare and probably occur in no more than 2% of the cases. BCL2 translocations may be secondary events in CLL. The prognostic implication of BCL2 translocations in CLL is uncertain, as the levels of protein expression are very high in cases lacking the translocation.

The nature of BCL2 translocations in CLL suggests a pathogenetic mechanism distinct from that seen in follicular non-Hodgkin's lymphoma. Unlike BCL2 translocations in follicular lymphoma, in CLL, most involve the IG light chain gene segments. The breakpoints within BCL2 are also different; most breakpoints in CLL involve the 5' region of the gene within the variant cluster region.

BCL3: Originally identified by its involvement in t(14:19)(q32;q13), BCL3 is a member of the IkB family of proteins, which mediates transcriptional up-regulation of NFkB target genes through interaction with p50/p52 homodimers. The translocation is not specific for CLL and occurs in several B-cell malignancies.

BCL11A: This gene, which encodes a Kr├╝ppel zinc finger protein, was cloned from its direct involvement in t(2;14)(p13;q32) in cases of aggressive CLL. How BCL11A transforms B cells remains unknown. It is a transcriptional repressor that binds directly to BCL6; however, BCL6 is not usually expressed at high levels, if at all, in CLL. BCL11A translocations are rare in CLL. All cases to date have retained germline IGHV segments, despite having undergone class switch recombination.

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