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Targeting trisomy 12 in chronic lymphocytic leukemia using molecular networks identified from pluripotent stem cells

ABSTRACT: Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in adults. While B cell-targeted therapies have revolutionized treatment, the underlying molecular targets of disease have not been addressed. A quarter of CLL patients have somatic trisomy 12 (tri12) which confers intermediate risk, and is otherwise embryonically lethal. Here, we report human pluripotent stem cells (PSC) harboring tri12 uniquely genocopy and phenocopy tri12 CLL. Using unbiased machine learning and transcriptomics, combined with chemical genomics, we reveal candidate tri12 gene networks and targets. These targets were validated to specifically reduce leukemic growth of tri12 CLL patient samples. Our study establishes a paradigm for using PSC to overcome barriers in revealing molecular networks involved in complex genetic abnormalities of human cancers such as tri12 CLL.

ORGANISM(S): Homo sapiens

PROVIDER: GSE133697 | GEO | 2021/07/01

REPOSITORIES: GEO

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