Related Experiment Video

Updated: Nov 8, 2025

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

413

Low dose venetoclax as a single agent treatment of plasma cell malignancies harboring t(11;14)

Hareth Nahi1,2,3, Muhammad Kashif1,2, Monika Klimkowska4,5

  • 1Department of Medicine, Karolinska Institutet, Stockholm, Sweden.

American Journal of Hematology
|April 26, 2021
PubMed

Insights

Venetoclax shows promising efficacy and manageable safety in patients with multiple myeloma (MM) and AL-amyloidosis harboring the t(11;14) translocation. Higher BCL2/MCL1 ratios correlated with better responses to BCL2 inhibitor therapy.

Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Approximately 20% of newly diagnosed multiple myeloma (NDMM) patients have the t(11;14) translocation, associated with poorer prognosis and CCND1 upregulation.
  • Patients with t(11;14) multiple myeloma (MM) show sensitivity to the BCL2 inhibitor venetoclax.
  • The t(11;14) translocation is linked to an increased BCL2/MCL1 protein expression ratio.

Purpose of the Study:

  • To investigate the safety and efficacy of venetoclax in patients with multiple myeloma (MM) and AL-amyloidosis harboring the t(11;14) translocation.
  • To analyze the correlation between BCL2 family member expression, clinical response, and treatment outcomes.
  • To identify potential mechanisms of resistance to venetoclax in t(11;14) positive hematologic malignancies.

Main Methods:

  • A cohort of 25 patients with multiple myeloma (MM) and AL-amyloidosis harboring t(11;14) received daily venetoclax (400 mg).
  • Efficacy was assessed by response rate (RR) and duration of treatment.
  • Immunohistochemistry (IHC) and RNA sequencing (RNASeq) were used to analyze BCL2 family expression and gene expression patterns at diagnosis and relapse.

Main Results:

  • Venetoclax treatment demonstrated manageable safety and promising efficacy, with partial responses or better observed in 44% of patients.
  • Responding patients exhibited significantly higher BCL2/MCL1 and BCL2/BCL-XL ratios.
  • The response rate (RR) for single-agent venetoclax was 71% in AL-amyloidosis and 33% in MM; IHC was useful for predicting outcomes.

Conclusions:

  • Venetoclax is an effective treatment option for multiple myeloma (MM) and AL-amyloidosis patients with the t(11;14) translocation.
  • Elevated BCL2/MCL1 ratio is a predictive biomarker for venetoclax response.
  • Downregulation of IRF5-targeted genes may represent a resistance mechanism that can be therapeutically targeted.

More Related Videos

Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography09:34

Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography

Published on: February 17, 2022

3.6K
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant08:52

Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant

Published on: May 27, 2011

17.4K

Related Concept Videos

Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.5K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.0K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.5K
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
8.9K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
277
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
271