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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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B-cell Function Gene Mutations in Diffuse Large B-cell Lymphoma: A Retrospective Cohort Study.

Peng-Peng Xu1, Hui-Juan Zhong1, Yao-Hui Huang1

  • 1State Key Laboratory of Medical Genomics; Shanghai Institute of Hematology; Shanghai Rui Jin Hospital; Shanghai Jiao Tong University School of Medicine; 197 Rui Jin Er Road, Shanghai, China.

Ebiomedicine
|February 4, 2017
PubMed
Summary

B-cell function gene mutations are common in diffuse large B-cell lymphoma (DLBCL) and impact treatment response. Rituximab consolidation can overcome adverse effects of BCRs mutations, improving outcomes for DLBCL patients.

Keywords:
B-cell function gene mutationsDiffuse large B-cell lymphomaPrognosisRituximab

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Area of Science:

  • Oncology
  • Genetics
  • Hematology

Background:

  • Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous non-Hodgkin lymphoma.
  • Next-generation sequencing has identified recurrent gene mutations in DLBCL.
  • Understanding these mutations is crucial for targeted therapies and improved patient outcomes.

Purpose of the Study:

  • To investigate the clinical relevance of B-cell function gene mutations in Chinese DLBCL patients.
  • To identify specific gene mutations associated with treatment response and prognosis.
  • To evaluate the impact of rituximab consolidation on patients with B-cell function gene mutations.

Main Methods:

  • Clinical analysis of 680 DLBCL patients treated with R-CHOP.
  • Targeted sequencing of B-cell function genes (BCRs, TLRs, TNFR pathways) in 275 patients.
  • Correlation analysis between gene mutations, clinical characteristics, and treatment outcomes (CR, PFS).

Main Results:

  • B-cell function gene mutations were found in 44.0% of DLBCL patients.
  • TLRs and TNFR pathway mutations were more frequent in non-complete response (non-CR) patients.
  • BCRs pathway mutations, revised IPI, and BCL-2/MYC expression independently predicted shorter progression-free survival (PFS).

Conclusions:

  • B-cell function gene mutations contribute to the molecular heterogeneity of DLBCL.
  • Specific mutations, particularly in BCRs pathway, are associated with poor prognosis.
  • Rituximab consolidation can mitigate the adverse prognostic impact of BCRs mutations in DLBCL.