A 60-year-old man undergoes lymph node biopsy due to persistent cervical lymphadenopathy. Histologic examination reveals a population of small lymphoid cells arranged in a follicular pattern. The cells demonstrate overexpression of the BCL2 gene. The protein encoded by this gene normally inhibits which of the following processes?

Question

A 60-year-old man undergoes lymph node biopsy due to persistent cervical lymphadenopathy.  Histologic examination reveals a population of small lymphoid cells arranged in a follicular pattern.  The cells demonstrate overexpression of the BCL2 gene.  The protein encoded by this gene normally inhibits which of the following processes?

Quizplus · Accepted Answer

11ec160b_3990_6bb6_9249_07a1510bfc95_MD0001_00 Apoptosis (ie, programmed cell death) is a strictly controlled method of cell death that allows for the degradation and removal of cells without evoking an inflammatory response. BCL2 protein functions as an inhibitor of the intrinsic (ie, mitochondrial) apoptotic pathway. Apoptosis involves triggering a cascade of proteolytic caspase enzymes. In the mitochondrial pathway, caspase activation occurs via the movement of cytochrome c protein from the mitochondrial intermembrane space to the cytoplasm. The BCL2 protein family regulates the ability of cytochrome c to permeate the mitochondrial outer membrane. This protein family includes both proapoptotic members (eg, BAX, BAK), which increase the permeability of the membrane via pore formation, and antiapoptotic members (eg, BCL2, BCL-XL), which preserve membrane integrity and prevent the release of cytochrome c. The characteristic cytogenetic abnormality associated with follicular lymphoma, a mature B-cell lymphoma, is a translocation involving the BCL2 gene on chromosome 18 and the immunoglobulin heavy-chain gene on chromosome 14 [t(14;18)]. This results in overexpression of BCL2 protein, which allows the neoplastic cells to evade apoptosis. (Choice B) Mutations of genes responsible for DNA mismatch repair (eg, MSH2) can be seen in disorders such as hereditary nonpolyposis colon cancer (ie, Lynch syndrome). This condition is characterized by a familial predisposition to colon cancer and other visceral malignancies (eg, endometrial cancer). (Choice C) Retinoblastoma (Rb) is a tumor suppressor protein that regulates cell cycle progression. When active, Rb binds E2F transcription factors, prevents transcription, and blocks progression through the G1/S checkpoint. (Choice D) RAS protein is a component of the mitogen-activated protein (MAP) kinase pathway, a signaling system that regulates cell proliferation via transmission of stimuli from the cell surface receptor to the nucleus. Neurofibromin, encoded by the NF1 gene, is a tumor suppressor protein that inhibits RAS function. (Choice E) Telomeres are DNA sequences found at the ends of chromosomes that are shortened with cellular division, eventually leading to growth arrest. Telomerase is an RNA-dependent DNA polymerase that prevents shortening of telomeres. The majority of cancer cells show increased telomerase activity, thereby avoiding growth arrest and facilitating continuous cell proliferation. Educational objective: BCL2 protein inhibits apoptosis by blocking the release of proapoptotic factors (eg, cytochrome c protein) from the mitochondria. BCL2 is overexpressed in follicular lymphoma secondary to the t(14;18) translocation involving BCL2 and immunoglobulin heavy-chain genes.

A 60-Year-Old Man Undergoes Lymph Node Biopsy Due to Persistent