Related Experiment Video

Updated: Oct 18, 2025

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
05:32

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

Published on: January 7, 2019

7.0K

Multiple Myeloma Relapse Is Associated with Increased NFκB Pathway Activity and Upregulation of the Pro-Survival

Ingrid Spaan1, Anja van de Stolpe2, Reinier A Raymakers3

  • 1Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The Netherlands.

Cancers
|September 28, 2021
PubMed

Insights

Multiple myeloma (MM) plasma cells show increased NFκB pathway activity upon relapse, correlating with BCL2A1 expression. Targeting BFL-1 may overcome therapy resistance in relapsed/refractory MM patients.

Area of Science:

  • Hematological Malignancies
  • Cancer Cell Signaling
  • Molecular Biology

Background:

  • Multiple myeloma (MM) is an incurable blood cancer characterized by therapy resistance and relapse.
  • NFκB signaling promotes MM growth, progression, and survival by regulating pro-survival BCL-2 proteins.
  • The role of BFL-1 (encoded by BCL2A1) in MM is debated due to its downregulation during B cell differentiation.

Purpose of the Study:

  • To quantify NFκB pathway activity in primary MM plasma cells (PC) across disease stages using a computational model.
  • To investigate the relationship between NFκB activity, disease progression, prognosis, and therapy outcomes in MM.
  • To explore the potential role of BFL-1 in therapy resistance during MM relapse.

Main Methods:

  • Utilized the signal transduction pathway activity (STA) computational model to assess NFκB pathway output.
  • Analyzed primary MM PC from diverse patient subsets at various disease stages.
  • Correlated NFκB pathway activity and BCL2A1 expression with clinical outcomes, including relapse and therapy response.

Main Results:

  • NFκB pathway activity remained unchanged during MM disease development and did not predict prognosis or therapy outcome.
  • Relapsed MM PC exhibited significantly increased NFκB pathway activity compared to pre-treatment samples.
  • Increased NFκB activity in relapsed MM correlated with elevated BCL2A1 expression in a subset of patients.

Conclusions:

  • NFκB pathway activity is not a reliable biomarker for MM progression or initial therapy response.
  • Upregulation of BFL-1, alongside BCL-XL and BCL-2, may contribute to therapy resistance in relapsed MM.
  • Targeting BFL-1 presents a potential therapeutic strategy for overcoming resistance in relapsed/refractory MM.
Keywords:
BCL2A1BFL-1NFκB signaling pathwaypro-survival BCL-2relapsed/refractory multiple myelomasignal transduction pathway activity

More Related Videos

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α11:27

A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α

Published on: November 2, 2018

9.3K
NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells10:57

NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells

Published on: January 12, 2020

10.8K

Related Concept Videos

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...
7.9K
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...
7.1K
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...
4.7K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.8K
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...
2.3K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K