‼️Excited to share my first preprint in the Stegmaier lab – using metabolite depletion screens in physiological culture medium and in vitro/in vivo CRISPR screens, we identify metabolism of vitamin B2 (riboflavin) as a potent dependency in acute myeloid leukemia (AML). A 🧵….

Grateful to Kim and everyone in the @KStegmaier_DFCI, @mvh_lab lab, @broadinstitute GPP and all other collaborators. Excited for any feedback!.

We're continuing to explore the idea of exploiting RF metabolism as an anti-cancer strategy, by leveraging a window of therapeutic opportunity where chemical targeting/dietary starvation of RF metabolism can sensitize to other anti-neoplastic agents.

Finally, we leveraged reporting that loss of ETC activity sensitizes to BCL-2 inhibition. As RF metabolism perturbation collapses the ETC, we found that AMLs are strongly sensitized to the BCL-2 inhibitor venetoclax upon chemical/genetic targeting of RFK or RF starvation.

We also showed that RF metabolism perturbation causes nucleotide imbalance via pyrimidine depletion and DNA damage. Strikingly, perturbing RF metabolism also impairs proteins that require iron-sulfur (Fe-S) clusters, a family of ancient cofactors.

Perturbing RF metabolism impaired cellular respiration, consistent with known roles of RF cofactors (FMN and FAD) in electron transfer in the electron transport chain. Interestingly, loss of RF not only ablates ETC function, but causes structural disassembly of Complex I and II.

Using metabolite depletion screens in AML cells and a culture medium designed to mimic human plasma, we identify that vitamin B2 (riboflavin, RF) is required for AML growth. Mining DepMap and our own CRISPR screens, we identify riboflavin kinase (RFK) as a dependency in AML.

Metabolism of vitamins has fascinating evolutionary history in humans, as we have long lost the ability to synthesize them de novo. We thus rely largely on dietary acquisition. We also really do not know (comprehensively) how vitamins are utilized by cancers, such as AML.

RT @DanaFarber: Congratulations to Kimberly Stegmaier, MD, on her appointment to the National Cancer Advisory Board. Co-director of Dana-Fa….

If you are at the @EHA_Hematology #EHA2024 congress, pencil in the YERM meeting tomorrow in Hall Mallo. We’ve put together an awesome program spanning all the most exciting topics in haematology with some truly stellar speakers. See you there! 🩸.

Ever wondered how nucleotide metabolism and cell fate decisions are linked in leukemia? Congrats Brian @BrianTDo1, Peggy @PeggyPHsu, Matt @mvh_lab et al on a beautiful piece of work tackling this complex problem – happy that @KStegmaier_DFCI and I could play a small part!.

RT @JohnstoneRicky: Congrats to Coner Kearney, Mario Djajawi, and @PijpersLizzy for this beautiful study. Awesome collaboration between @P….

RT @KStegmaier_DFCI: Congrats to Shan Lin recipient of the LLS-CDP fellow achievement award and Stefan Bjelosevic a new LLS fellow. So prou….

Thank you @LLSusa @LLSResearch and @KStegmaier_DFCI for your faith and support of my career. Hugely appreciative as we endeavour to find new modalities for treating high risk #pediatric #AML.

RT @DFBC_PedCare: We are pleased to announce that.@usnews (@USNewsHealth) has named DF/BC Cancer and Blood Disorders Center the #2 program….

Reflecting on a brilliant @EHA_Hematology #EHA2023 Congress this year. Got to meet my fellow @young_eha committee members in person (finally!), see and hear some awesome science, and formed some lasting friendships. See you next year #EHA2024 in Madrid!!

What an amazing session!! Thanks to all that came but particularly the brilliant speakers and my co-chair Filipa! @young_eha @EHA_Hematology #EHA2023.

After 3 years (2 of which locked in Fortress Australia during COVID), finally made it to my first in-person @EHA_Hematology #EHA2023 Congress! Enjoying an action packed @young_eha #YERM2023 to kick us off!

RT @EHA_Hematology: #EHA has landed in Frankfurt! Starting tomorrow, you can immerse yourself in the latest clinical and translational rese….

RT @JohnstoneRicky: The @JohnstoneLab are hiring a postdoc! Interested in cancer epigenetics, transcription and immunology? Want to join a….