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Updated: Feb 13, 2026
Immunoglobulin Gene Sequence Analysis In Chronic Lymphocytic Leukemia: From Patient Material To Sequence Interpretation
Published on: November 26, 2018
Potential of BCL2 as a target for chronic lymphocytic leukemia treatment
Riccardo Moia1, Fary Diop1, Chiara Favini1
1a Division of Hematology, Department of Translational Medicine , University of Eastern Piedmont , Novara , Italy.
Introduction:
Chronic lymphocytic leukemia (CLL) is a highly heterogeneous disease. Deregulation of apoptosis is a major pathogenetic feature, and represents a therapeutic target. TP53 disrupted patients are categorized as high risk patients and are treated with novel target therapies. Among these new drugs, venetoclax, an orally bioavailable BCL2 inhibitor, has shown high efficacy also in relapsed/refractory CLL with TP53 disruption. Venetoclax has also been tested in combination with other drugs without compromising venetoclax dose and with a good safety profile. Areas covered: This article covers the biology of apoptosis in CLL from a translational viewpoint and deals with the mode of action of BCL2 inhibitors, in particular venetoclax. On this biological rationale, the review then focuses on the results obtained in clinical trials with venetoclax in CLL. Expert commentary: The availability of venetoclax represents a major advance in CLL treatment and offers new opportunities to further improve the results obtained until now by combining venetoclax with other agents. Venetoclax has achieved responses also in patients with TP53 disruption. These results strongly suggest that the mechanism by which venetoclax kills CLL cells might overcome a dysfunctional TP53 that is a major hallmark of chemorefractoriness to conventional antineoplastic agents.
Insights
Venetoclax, a BCL2 inhibitor, shows high efficacy in treating chronic lymphocytic leukemia (CLL), including high-risk TP53-disrupted patients. This targeted therapy offers new treatment opportunities for relapsed/refractory CLL.
Area of Science:
- Translational oncology
- Molecular biology of apoptosis
- Hematologic malignancies
Background:
- Chronic lymphocytic leukemia (CLL) is characterized by apoptosis deregulation, a key pathogenetic feature and therapeutic target.
- TP53 disruption defines high-risk CLL patients, necessitating novel therapeutic strategies.
- Venetoclax, a BCL2 inhibitor, demonstrates significant efficacy in relapsed/refractory CLL, particularly in TP53-disrupted cases.
Purpose of the Study:
- To review the biology of apoptosis in CLL from a translational perspective.
- To elucidate the mechanism of action of BCL2 inhibitors, specifically venetoclax.
- To summarize clinical trial outcomes of venetoclax in CLL treatment.
Main Methods:
- Review of scientific literature on apoptosis in CLL.
- Analysis of the mode of action of BCL2 inhibitors.
- Synthesis of data from clinical trials involving venetoclax in CLL patients.
Main Results:
- Venetoclax exhibits high efficacy in relapsed/refractory CLL, including TP53-disrupted patients.
- Combination therapies with venetoclax show a good safety profile without dose compromise.
- Venetoclax responses in TP53-disrupted CLL suggest overcoming TP53-mediated chemoresistance.
Conclusions:
- Venetoclax represents a significant advancement in CLL treatment, offering improved outcomes.
- Combination strategies involving venetoclax hold promise for further enhancing therapeutic results.
- Venetoclax's efficacy in TP53-disrupted CLL highlights its potential to overcome conventional treatment resistance.
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