Publications by authors named "T Mercher"
Pediatric acute myeloid leukemia frequently harbor fusion oncogenes associated with poor prognosis, including KMT2A, NUP98 and GLIS2 rearrangements. While murine models have demonstrated their leukemogenic activities, the steps from a normal human cell to leukemic blasts remain unclear. Here, we precisely reproduced the inversion of chromosome 16 resulting in ETO2::GLIS2 fusion in human induced pluripotent stem cells (iPSC).
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- The study investigates the role of the ETO2::GLIS2 fusion oncogene in pediatric acute myeloid leukemia (AML), highlighting its connection to worse outcomes in patients.
- The researchers developed models using lentiviral transduction and CRISPR-Cas9 to explore how ETO2::GLIS2 influences leukemia development in human fetal versus post-natal hematopoietic stem cells.
- They found that the presence of specific human cytokines like IL3 and SCF is crucial for leukemogenesis, suggesting that a combination treatment targeting MEK and BCL2 could effectively reduce leukemia progression.
Transcriptional cofactors of the ETO family are recurrent fusion partners in acute leukemia. We characterized the ETO2 regulome by integrating transcriptomic and chromatin binding analyses in human erythroleukemia xenografts and controlled ETO2 depletion models. We demonstrate that beyond its well-established repressive activity, ETO2 directly activates transcription of MYB, among other genes.
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