Exploring the mechanisms of Venetoclax resistence via drug screening and genome-wide CRISPR screening.

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Authors	LADUNGOVÁ Adriana PESCHELOVÁ Helena DOSTÁLOVÁ Lenka LODHI Yusuf GOTTUMUKKALA Narendra Varma MAYER Jiří ŠMÍDA Michal
Year of publication	2023
Type	Conference abstract
MU Faculty or unit	Central European Institute of Technology
Citation
Attached files	65th_ASH_Annual_Meeting2023.pdf
Description	Combining Venetoclax, a selective BCL-2 inhibitor, with hypomethylating agents has revolutionized frontline acute myeloid leukemia (AML) treatment. Despite its success, the occurrence of resistance remains a significant concern, limiting the range of available treatment alternatives. Little is known about the mechanism by which the cells escape the treatment. Recent studies have observed MCL1 upregulation in AML cells to promote resistance, and the rationale to use an MCL1 inhibitor became attractive. Although MCL1 inhibitors work exceptionally well in vitro their clinical trials were unsuccessful due to their toxicity. Here, we aim to identify other genes responsible for acquiring resistance and tackle the problem through screening for clinically approved drugs to rapidly benefit the patients with our study.
Related projects:	Specifický výzkum v oblasti „Life Sciences“ Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit IX National institute for cancer research