Thank you very much Julia!

Check out the latest ISEH preprint blog! Thanks ISEH for the featured interview.

Last but not least, we appreciate the support of our funding source NCI, DamonRuyon and DorisDuke, towards this work Thanks to a terrific collaborative effort with ColumbiaCancer, CSCI, MSK, Cleveland Clinic, and Erasmus MC. @thedoctorisvin.bsky.social

Overall, we identify enhanced FLI1 chromatin accessibility as a driver of stemness and leukemic transformation in STAG2 mutant leukemia. These further highlight how chromatin architecture change can engage oncogenic transcription factor to drive leukemogenesis and therapeutic response. 10/10

Lastly, we demonstrate that the Stag2 mutant induces chromatin changes that influence the MEN1 binding at HOX loci and sensitize leukemia cells towards Revumenib. 9/10

To understand the pre-leukemic initiation of Stag2 mutant setting, we generate a Stag2 mutant leukemic mouse model where we pinpoint FLI1 accessibility increased in the expanded myeloid biased progenitors with defective differentiation. 8/10

Subsequently, we can reverse the upregulation of CD34 with knock-down of FLI1. 7/10

Phenotypically, this leads to upregulation of CD34 (human hematopoietic stem cell marker), which coincides with clinical presentation of STAG2 mutant leukemia, as well as transcription program. 6/10

We then find Stag2 also regulates the FLI1 chromatin accessibility in leukemia, which leads to aberrant binding of FLI1 at cis-regulatory elements. 5/10

Here, we identify that chromatin in HSPCs is more open for FLI1 targeting sites and Stag2 regulates the FLI1 chromatin accessibility. 4/10

To understand how Stag2 cohesin affects stem cell function, we comprehensively assess the dynamic chromatin changes associated with HSPC to myeloid progenitor transition. 3/10

Stag2 cohesin controls 3D genome organization with CTCF and transcription factors important for hematopoietic stem and progenitor cell function. It frequently mutates in myelodysplastic syndromes and acute myeloid leukemia. But how it contributes to leukemia development is unknown. 2/10

My very first post on 🦋. 1. Do you know that cohesin ring controls how transcription factor (TF) access chromatin? Excited to share my first piece of postdoctoral work where we investigate how Stag2 cohesin contributes to leukemia! 1/10. www.biorxiv.org/content/10.1....