What is BCL2 rearrangement?

What is BCL2 rearrangement?

Detection of BCL2 rearrangement aids in diagnosis and classification of follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and other aggressive B-cell lymphomas in conjunction with clinical, morphologic, and flow cytometric data. The most frequent rearrangement partner is IgH (14q32).

Where is BCL2 found?

BCL2 is normally located on chromosome 18q21. 33 in a telomere to centromere orientation. The molecular consequence of the t(14;18) juxtaposes of the BCL2 gene next to IGH locus on the der(14) chromosome, in the same transcriptional orientation as the IGH gene.

What is the role of BCL2 in apoptosis?

BCL2 prevents BAX/BAK oligomerization, which would otherwise lead to the release of several apoptogenic molecules from the mitochondrion. It is also known that BCL2 binds to and inactivates BAX and other pro-apoptotic proteins, thereby inhibiting apoptosis.

Is BAX a BCL2?

BAX is a member of the Bcl-2 gene family. BCL2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities.

What is BCL6 rearrangement?

BCL6 (3q27) rearrangement is the most frequent chromosomal abnormality in diffuse large B-cell lymphoma (DLBCL). Previously, studies on the association between BCL6 rearrangement and DLBCL outcome remain controversial.

What stains BCL2?

Positive staining – normal. Lymph node: small B lymphocytes in mantle zone and cells within T cell areas. Adrenal cortex, melanocyties, thymus-medullary cells, thyroid gland solid cell nests. Immature (but not mature) small ganglion cells.

How does Bcl-2 promote apoptosis?

The Bcl-2 family is the best characterized protein family involved in the regulation of apoptotic cell death, consisting of anti-apoptotic and pro-apoptotic members. After entering the cytoplasm, cytochrome c and AIF directly activate caspases that cleave a set of cellular proteins to cause apoptotic changes.

What is Bax Bcl-2 ratio?

Bax/Bcl-2 ratio can act as a rheostat which determines cell susceptibility to apoptosis [21]. Lower levels of this ratio may lead to resistance of human cancer cells to apoptosis. Thus, Bax/Bcl-2 ratio can affect tumor progression and aggressiveness.

How does Bax get activated?

Bax and Bak are activated by BH3-only proteins and inhibited by prosurvival Bcl-2 proteins via direct interactions. Bax and Bak undergo major conformation changes during transition from inactive monomers to activated oligomers.

What chromosome is BCL6 on?

The BCL6 gene on chromosome 3q27 encodes a 96 kDa sequence-specific transcriptional repressor protein with 6 C-terminal zinc-finger motifs and an N-terminal POZ/ZIN domain homologous to a family of zinc-finger proteins.

Where does the protein Bcl-2 get its name from?

Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas.

Can a over expression of Bcl-2 cause cancer?

The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma.

Are there any small molecule inhibitors of Bcl-2?

In the mid-2000s, Abbott Laboratories developed a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. This compound is part of a group of BH3 mimetic small molecule inhibitors (SMI) that target these Bcl-2 family proteins, but not A1 or Mcl-1.

Where is Bcl-2 located in the mitochondria?

BCL-2 is localized to the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins.