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Centrosome Amplification Is a Potential Molecular Target in Paediatric Acute Lymphoblastic Leukemia.


ABSTRACT: Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children, with most cases arising from fetal B cell precursor, termed B-ALL. Here, we use immunofluorescence analysis of B-ALL cells to identify centrosome amplification events that require the centrosome clustering pathway to successfully complete mitosis. Our data reveals that primary human B-ALL cells and immortal B-ALL cell lines from both human and mouse sources show defective bipolar spindle formation, abnormal mitotic progression, and cell death following treatment with centrosome clustering inhibitors (CCI). We demonstrate that CCI-refractory B-ALL cells exhibit markers for increased genomic instability, including DNA damage and micronuclei, as well as activation of the cyclic GMP-AMP synthase (cGAS)-nuclear fa

SUBMITTER: Guo M 

PROVIDER: S-EPMC9818390 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature