Premium
Role of Bcl‐2 in Hematological Cancer Formation
Author(s) -
Link Tina,
Fortier Abigail,
Jain Supriya,
Kepner Alisa,
Koh Ally,
Stanovski Lisa,
UlIslam Misha,
Walter Ellie
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.934.19
Subject(s) - cancer research , chromosomal translocation , apoptosis , chronic lymphocytic leukemia , venetoclax , lymphoma , biology , leukemia , cancer , follicular lymphoma , immunoglobulin heavy chain , downregulation and upregulation , cancer cell , antibody , gene , immunology , genetics
B cell leukemia/lymphoma 2 (BCL‐2) is a 26 kilodalton, amphipathic, anti‐apoptotic protein located on the outer mitochondrial membrane. BCL‐2 interacts with other anti‐apoptotic and pro‐apoptotic factors in order to regulate apoptosis. If a structural change occurs on the BCL‐2 gene, overexpression of the BCL‐2 protein can result. This causes a change in the ratio of BCL‐2 to its BCL‐2 Homologous 3 (BH3) ligands, preventing the release of the apoptotic signal. The primary change associated with BCL‐2 overexpression in lymphomas is a t(14;18) chromosomal translocation, which causes an increase in BCL‐2 transcription. The upregulation of the oncogene allows for the survival of the mutated B cells by raising the apoptotic threshold, which then dislodges regular lymphocytes in the bone marrow or lymph nodes. Lack of cell death due to overexpression of BCL‐2 has been linked to hematological malignancies, specifically lymphomas and myelomas. Both B‐lymphocytic cancers can result from alterations of the immunoglobulin heavy chain locus on chromosome 14. While BCL2 translocation can cause Follicular Lymphoma, BCL2 over‐expression is observed in many other tumor types and likely contributes to cancer progression and drug resistance in these tumors. Treatments to inhibit BCL‐2 include attempts at activation and overexpression of the pro apoptotic BH3 proteins, BCL‐2 Associated X Protein (BAX) and BCL‐2 Associated K protein (BAK), and creation of BH3 mimetics. Indeed, the FDA approved the BCL2 inhibitor Venetoclax (ABT‐199) earlier this year for the treatment of Chronic Lymphocytic Leukemia. These treatments could help cause cancer cell death by binding to targeted anti‐apoptotic proteins and causing the signal for apoptosis to be released. This could neutralize the cancerous effects of the BCL‐2 oncogene upregulation. Walton High School SMART (Students Modeling A Research Topic) Team used the computer program Jmol to create a 3D printed model of BCL‐2 and composed a review poster of our secondary research to investigate and demonstrate the relationship between the structure and function of this molecule. Support or Funding Information Diane Munzenmaier, Ph.D., Center for Biomolecular Modeling, Milwaukee School of Engineering