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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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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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VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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BCL2 Expression in First-Line Diffuse Large B-Cell Lymphoma Identifies a Patient Population With Poor Prognosis.

Elizabeth Punnoose1, Franklin V Peale1, Edith Szafer-Glusman1

  • 1Genentech Inc, South San Francisco, CA.

Clinical Lymphoma, Myeloma & Leukemia
|December 11, 2020
PubMed
Summary
This summary is machine-generated.

This study developed a BCL2 immunohistochemistry assay to identify diffuse large B-cell lymphoma (DLBCL) patients who may benefit from BCL2 inhibitors. BCL2 expression in DLBCL indicates a poorer prognosis, supporting its use in patient selection for clinical trials.

Keywords:
ABC DLBCL subtypeBiomarkersCell of originGCB DLBCL subtypeImmunohistochemistry

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Area of Science:

  • Oncology
  • Hematology
  • Immunohistochemistry

Background:

  • B-cell lymphoma 2 (BCL2) expression is a potential therapeutic target in diffuse large B-cell lymphoma (DLBCL).
  • Accurate assessment of BCL2 protein expression is crucial for identifying patient populations for BCL2 inhibitor clinical development.

Purpose of the Study:

  • To develop a reproducible immunohistochemistry (IHC) algorithm and assay for quantifying BCL2 protein expression in de novo DLBCL.
  • To evaluate the prognostic value of BCL2 expression in DLBCL patients treated with immunochemotherapy.

Main Methods:

  • A prospective algorithm incorporating BCL2 staining intensity and percentage of positive cells was developed.
  • The assay's reproducibility was validated across multiple laboratories.
  • Prognostic impact was assessed in 3 large DLBCL cohorts (MAIN, GOYA, and a population-based registry) using multivariate analyses.

Main Results:

  • Approximately 50% of DLBCL tumors exhibited BCL2 positivity, more frequent in high International Prognostic Index (IPI) and activated B-cell-like subtypes.
  • BCL2 expression was significantly associated with poorer progression-free survival (PFS) across all studied cohorts.
  • Patients with BCL2-positive and high IPI DLBCL demonstrated the poorest PFS outcomes.

Conclusions:

  • The developed BCL2 IHC scoring system and assay are reliable for patient selection.
  • BCL2 positivity is a significant negative prognostic marker in DLBCL.
  • This assay can facilitate the enrollment of appropriate patients in future BCL2 inhibitor clinical trials.