Related Experiment Video

Updated: Jan 25, 2026

Bioprinting of Hydrogel Tumor Slices as a 3D Model for Mantle Cell Lymphoma
08:31

Bioprinting of Hydrogel Tumor Slices as a 3D Model for Mantle Cell Lymphoma

Published on: September 12, 2025

789

BCL2 Amplicon Loss and Transcriptional Remodeling Drives ABT-199 Resistance in B Cell Lymphoma Models

Xiaohong Zhao1, Yuan Ren1, Matthew Lawlor2

  • 1Chemical Biology and Molecular Medicine Program, Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA.

Cancer Cell
|May 16, 2019
PubMed

Insights

Drug-tolerant persister cells drive resistance to BCL-2 inhibitor ABT-199 in lymphomas. Targeting transcriptional reprogramming, particularly cyclin-dependent kinase 7 (CDK7), offers a new strategy to overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Drug-tolerant persister tumor cells are a key factor in the development of drug resistance and disease relapse.
  • Resistance to BCL-2 inhibitors like ABT-199 is a significant challenge in treating certain lymphomas.

Purpose of the Study:

  • To investigate the mechanisms underlying ABT-199 resistance in mantle cell lymphoma and double-hit lymphoma models.
  • To identify vulnerabilities in drug-tolerant persister cells that can be targeted to overcome resistance.

Main Methods:

  • Utilized lymphoma models to study ABT-199 resistance.
  • Performed pharmacoproteomic and pharmacogenomic screens.
  • Analyzed adaptive super-enhancer remodeling and transcriptional reprogramming.

Main Results:

  • ABT-199 resistance emerged from persister clones with loss of 18q21 amplicons harboring BCL2.
  • Persister status was linked to adaptive super-enhancer remodeling that altered transcription.
  • Persister cells showed vulnerability to inhibition of transcriptional machinery, especially CDK7.

Conclusions:

  • Targeting transcriptional reprogramming, particularly CDK7, can overcome ABT-199 resistance in B-cell lymphomas.
  • Transcription-targeting agents represent a promising therapeutic approach for disabling drug resistance.
Keywords:
ABT-199BCL2CDK7THZ1double-hit lymphomadrug persisterdrug resistancemantle cell lymphomasuper-enhancer remodelingtranscriptome reprogramming

More Related Videos

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma10:52

Tumor Engraftment in a Xenograft Mouse Model of Human Mantle Cell Lymphoma

Published on: March 30, 2018

11.6K
Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma08:53

Flow-sorting and Exome Sequencing of the Reed-Sternberg Cells of Classical Hodgkin Lymphoma

Published on: June 10, 2017

10.4K

Related Concept Videos

Nucleosome Remodeling02:54

Nucleosome Remodeling

Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
10.8K
Transcription Elongation Factors02:35

Transcription Elongation Factors

Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.5K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
Transcription01:10

Transcription

Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
155.8K
Line Loss01:10

Line Loss

The different configurations of source-load connections include wye (star) and delta connections. The relationship between line and phase voltages and currents varies depending on the configuration. When the source is supplying power, it is transmitted through the wires to the load, and during this transmission, some power is absorbed by the wires, leading to line loss.
Line loss impacts power delivery efficiency in a balanced three-phase circuit. The symmetry in such a circuit simplifies the...
518
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.3K