Targeting WEE1 and asciminib suppresses ABL-tyrosine kinase inhibitor-resistant chronic myeloid leukemia cells.

ABSTRACT:

Background

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of white blood cells. Tyrosine kinase inhibitors (TKIs) are the standard treatment; however, resistance to BCR::ABL1 mutations remains challenging. WEE1, a checkpoint kinase involved in mitosis and DNA repair, is a potential therapeutic target for CML treatment.

Methods

Ponatinib-resistant CML cells were screened to identify candidates for overcoming drug resistance. The efficacy of the ABL TKI asciminib and the WEE1 inhibitor MK-1775 was evaluated using proliferation and colony formation assays. Public database analysis (GSE100026) assessed WEE1/PKMYT1 expression in CML.

Results

In vitro screening identified MK-1775 as a promising therapeutic can

SUBMITTER: Okabe S 

PROVIDER: S-EPMC12238689 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature