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Association details:
Evidence:
Evidence Level:
Resistant: D – Preclinical
Source:
Title:

Investigation of New Therapeutic Compounds for Juvenile Myelomonocytic Leukemia Using Induced Pluripotent Stem Cells with Stably Activated Ras Pathway

Published date:
11/06/2019
Excerpt:
As in vitro models of JMML, we generated inducible pluripotent stem cells (iPSC) stably expressing wildtype or activating oncogenic versions of KRAS (G12D) or NRAS (G13D) as well as iPSCs with CRISPR interference mediated downregulated NF1 expression…In our screen the model cell lines were resistant to all tested MEK-inhibitors, including Selumetinib and Trametinib. The broad receptor tyrosine kinase inhibitor Dovitinib and the DNA methyltransferase inhibitor Azacytidine elicited strong responses in all iPSC cell lines regardless of their KRAS, NRAS or NF1 state.
DOI:
https://doi.org/10.1182/blood-2019-131406