2022
DOI: 10.1371/journal.pcbi.1010439
|View full text |Cite
|
Sign up to set email alerts
|

An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia

Abstract: The over-expression of the Bcl-2 protein is a common feature of many solid cancers and hematological malignancies, and it is typically associated with poor prognosis and resistance to chemotherapy. Bcl-2-specific inhibitors, such as venetoclax, have recently been approved for the treatment of chronic lymphocytic leukemia and small lymphocytic lymphoma, and they are showing promise in clinical trials as a targeted therapy for patients with relapsed or refractory acute myeloid leukemia (AML). However, successful… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1

Citation Types

0
1
0

Year Published

2023
2023
2024
2024

Publication Types

Select...
2

Relationship

0
2

Authors

Journals

citations
Cited by 2 publications
(1 citation statement)
references
References 163 publications
0
1
0
Order By: Relevance
“…Due to its relevance, the biological basis for Venetoclax resistance has been extensively studied. To date we can identify the main mechanisms involved (Figure 2): occurrence of Bcl-2 mutations (e.g., Gly101Va) that cause a reduction in Venetoclax affinity for Bcl-2 [117], upregulation of other anti-apoptotic proteins like BCL-XL or MCL-1, which can provide alternative survival signals for the leukemia cells [118], reduced expression of proapoptotic proteins crucial for Venetoclax-induced apoptosis [119], and increased OXPHOS or alternative sources for energy metabolism [120]. To overcome resistance to Venetoclax in leukemia, a variety of approaches are under investigation.…”
Section: Targeting Bcl-2 Proteins In Amlmentioning
confidence: 99%
“…Due to its relevance, the biological basis for Venetoclax resistance has been extensively studied. To date we can identify the main mechanisms involved (Figure 2): occurrence of Bcl-2 mutations (e.g., Gly101Va) that cause a reduction in Venetoclax affinity for Bcl-2 [117], upregulation of other anti-apoptotic proteins like BCL-XL or MCL-1, which can provide alternative survival signals for the leukemia cells [118], reduced expression of proapoptotic proteins crucial for Venetoclax-induced apoptosis [119], and increased OXPHOS or alternative sources for energy metabolism [120]. To overcome resistance to Venetoclax in leukemia, a variety of approaches are under investigation.…”
Section: Targeting Bcl-2 Proteins In Amlmentioning
confidence: 99%