Related Experiment Video

Updated: Jun 18, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad

Anna Frenzel1, Verena Labi, Waldemar Chmelewskij

  • 1Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria.

Blood
|December 8, 2009
PubMed

Insights

Bcl-2 modifying factor (Bmf) and Bcl-2 antagonist of cell death (Bad) proteins suppress c-Myc-driven B-cell lymphomagenesis. Loss of Bmf, but not Bad, promotes B-cell lymphoma by inhibiting apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Immunology

Background:

  • Oncogenic c-Myc drives excessive cell proliferation balanced by apoptosis via p53-dependent and -independent pathways.
  • BH3-only proapoptotic Bcl-2 family members, including Bmf and Bad, are key regulators of apoptosis.

Purpose of the Study:

  • To investigate the roles of Bmf and Bad in antagonizing c-Myc-driven B-cell lymphomagenesis.
  • To elucidate the mechanisms by which Bmf and Bad influence tumor development and apoptosis.

Main Methods:

  • Utilized Emu-myc transgenic mice lacking Bmf or Bad.
  • Analyzed tumor formation, cell accumulation in hematopoietic organs, and immunophenotypes.
  • Assessed B-cell apoptosis and p53 pathway activation.

Main Results:

  • Bmf and Bad antagonize c-Myc-driven B-cell lymphomagenesis.
  • Loss of Bmf, but not Bad, promoted IgM(+) B-cell lymphoma by protecting against oncogene-induced apoptosis.
  • Bmf deficiency reduced the need for p53 inactivation, implicating it in a p53-independent pathway.

Conclusions:

  • Bmf and Bad are critical suppressors of c-Myc-driven B-cell lymphomagenesis.
  • Bmf acts as a p53-independent tumor suppressor by maintaining apoptosis in pre-malignant B cells.
  • Bad functions as a sentinel for trophic factor deprivation, impacting B-cell apoptosis levels.

More Related Videos

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice11:25

Busulfan as a Myelosuppressive Agent for Generating Stable High-level Bone Marrow Chimerism in Mice

Published on: April 1, 2015

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

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 daughter...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...