AI Article Synopsis
- Pediatric histiocytic neoplasms are blood disorders often caused by a mutation in the BRAF gene, specifically BRAF-V600E.
- Researchers discovered two new BRAF gene fusions (MTAP-BRAF and MS4A6A-BRAF) in aggressive cases that don't respond to a previously known treatment called PLX8394.
- The study suggests that instead of relying on PLX8394, using the broader RAF inhibitor LY3009120 and MEK inhibitors could effectively suppress growth driven by these new fusions.
Article Abstract
Pediatric histiocytic neoplasms are hematopoietic disorders frequently driven by the BRAF-V600E mutation. Here, we identified two BRAF gene fusions (novel MTAP-BRAF and MS4A6A-BRAF) in two aggressive histiocytic neoplasms. In contrast to previously described BRAF fusions, MTAP-BRAF and MS4A6A-BRAF do not respond to the paradox breaker RAF inhibitor (RAFi) PLX8394 due to stable fusion dimerization mediated by the N-terminal fusion partners. This highlights a significant and clinically relevant shift from the current dogma that BRAF-fusions respond similarly to BRAF-inhibitors. As an alternative, we show suppression of fusion-driven oncogenic growth with the pan-RAFi LY3009120 and MEK inhibition.
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| http://dx.doi.org/10.1002/pbc.28933 | DOI Listing |
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