Journal
BIOMARKER RESEARCH
Volume 9, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40364-021-00288-7
Keywords
Venetoclax; Acquired resistance; Acute myeloid leukemia
Categories
Funding
- National Natural Science Foundation of China [81800199]
- Natural Science Foundation of Zhejiang Province [LY21H080003]
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The study found that the mechanism of acquired VEN resistance in AML patients differs from CLL, where reconstructed existing gene mutations mainly contribute to VEN resistance. Precise mutation monitoring and targeted therapy may be effective strategies to prevent and overcome acquired VEN resistance in AML.
Y Venetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of >= 70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.
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