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Association details:
| Biomarker: | FLT3-ITD mutation + FLT3 D835 |
|---|---|
| Cancer: | Acute Myelogenous Leukemia |
| Drug: | Venclexta (venetoclax) (Bcl2 inhibitor) + Xospata (gilteritinib) (Multi-tyrosine kinase inhibitor) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Inhibition of BCL2A1 by STAT5 inactivation overcomes resistance to targeted therapies of FLT3-ITD/D835 mutant AML
Published date:
02/01/2022
Excerpt:
However, a type I TKI, gilteritinib, inhibited the expression of BCL2A1 through inactivation of STAT5 and alleviated TKI resistance of FLT3-ITD/D835. The combination of gilteritinib and venetoclax showed synergistic effects in the FLT3-ITD/D835 positive AML cells. The promoter region of BCL2A1 contains a BRD4 binding site. Thus, the blockade of BRD4 with a BET inhibitor (CPI-0610) downregulated BCL2A1 in FLT3-mutated AML cells and extended profound suppression of FLT3-ITD/D835 mutant cells. Therefore, we propose that BCL2A1 has the potential to be a novel therapeutic target in treating FLT3-ITD/D835 mutated AML.
DOI:
10.1016/j.tranon.2022.101354
Source:
Title:
BCL2A1: A Novel Target in Refractory/Relapsed AML with FLT3-ITD/D835 Double Mutations
Published date:
09/01/2021
Excerpt:
Gilteritinib targets BCL2A1 through inactivation of STAT5, and combinatorial gilteritinib and venetoclax were highly synergistic in FLT3-ITD/ D835 double-positive cells. Furthermore, inhibition of BRD4 with the BET inhibitor CPI-0610 exhibited anti-tumor activity in FLT3-ITD/D835 double-positive AML and suppressed BCL2A1 expression in these cells.
