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Review Question - QID 101457

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QID 101457 (Type "101457" in App Search)
A 40-year-old male presents to his primary care physician for a regularly scheduled check-up. Physical examination reveals nontender cervical lymphadenopathy. A biopsy of the lymph node reveals aggregates of follicular architecture, and cytogenic analysis shows a t(14;18) translocation. The protein most likely responsible for the patient’s condition does which of the following:

Regulates passage through the cell cycle

7%

27/375

Activates DNA repair proteins

4%

14/375

Provides mitotic cytoskeleton

2%

6/375

Inhibits apoptosis

78%

292/375

Regulates cell growth through signal transduction

8%

30/375

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The clinical presentation is consistent with that of follicular lymphomas. The oncogene Bcl-2 is found in 80-90% of follicular lymphomas. Bcl-2 inhibits apoptosis.

Follicular lymphoma presents as painless lymphadenopathy. Minor B-cell proliferation forms follicular aggregates that replace normal lymph node architecture. The disease is most commonly found in adults and may progress to large B cell lymphoma. The t(14;18) translocation is found in 80-90% of follicular lymphomas. The Ig-heavy chain locus of chromosome 14 is fused with BCL2 on chromosome 18, producing bcl-2 (B-cell lymphoma 2) overexpression.

Freedman reviews the diagnosis of follicular lymphoma, reporting that the diagnosis is based on histology, preferably of biopsy of a lymph node. Immunohistochemical staining is positive in virtually all cases for cytoplasmic expression of bcl-2 protein. The overwhelming majority of cases have the characteristic t(14;18) translocation involving the IgH/bcl-2 genes.

Nambiar et al. review the molecular biology of Bcl-2. They report the t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Breaks in chromosome 18 are localized at the 3'-UTR of BCL2 gene or downstream and are mainly clustered in either the major breakpoint region or the minor breakpoint cluster region (mcr). The recombination activating gene (RAG) complex induces breaks at IgH locus of chromosome 14, whereas the mechanism of fragility at BCL2 mcr remains unclear.

Illustration A shows the follicular architecture of follicular lymphoma.

Incorrect Answers:
Answers 1: p53 and c-myc are two proteins that regulate passage through the cell cycle.
Answer 2: p53 is a protein that can activate DNA repair proteins.
Answer 3: Microtubules compose the cytoskeleton during mitosis.
Answer 5: Tyrosine kinases are a group of proteins known to regulate cell growth through signal transduction.
NOTE: None of the above proteins are implicated in follicular lymphoma or associated with t(14;18) translocation

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