iiinova — where your digital self keeps evolving

lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

A big thanks to our teams, all our collaborators, funding bodies @inserm.fr @fondationarc.bsky.social #INCa @erc.europa.eu and others, our great hosting institutions @institut-leucemie.bsky.social and of course a big thanks to #ScienceTranslationalMedicine @science.org for publishing our work !!

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lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

Bottom line: AML chemoresistance isn't only about new mutations — it can be about hijacking RNA splicing. Targeting PAK1 + CLK1/4 offers a promising combination strategy against relapse. Checkout all these data and much more !! 📄 🔗 www.science.org/doi/10.1126/...

science.org

Splicing-associated network PAK1-CLK1/4-SRRM1 is a vulnerability to overcome chemoresistance in human and mouse acute myeloid leukemia

Chemoresistance in acute myeloid leukemia depends on an active PAK1-CLK1/4-SRRM1 splicing network that can be targeted to prevent relapse.

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lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

Combining a PAK1 inhibitor (FRAX597) with a CLK inhibitor (TG003) mimicked SRRM1 loss, resensitized resistant cells to chemo, and improved outcomes in mouse and patient-derived xenograft leukemia models.

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lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

SRRM1 itself is not druggable — but it's controlled by two druggable kinase families, PAK1 and CLK1/4, both hyperactive in resistant cells. We even found a PAK1 mutation (A477S) that emerged specifically at relapse in one patient, making the kinase constitutively active.

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lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

That "elsewhere" was splicing. Resistant cells showed rewiring of alternative splicing in mouse and AML patients at relapse. An in vivo screen pointed to SRRM1, a spliceosome protein, its inhibition hurt chemo-resistant cells (mouse and human) much more than chemo-sensitive ones.

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lobrylab.bsky.social @lobrylab.bsky.social · 08/07/2026

AML has a frustrating pattern: most patients reach remission, but most relapse with chemoresistant disease. To get insights into this we built a mouse model that becomes chemoresistant — mimicking the clinic. No new mutations appeared, so resistance had to come from elsewhere.

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Reposted by @lobrylab.bsky.social

Alex Puissant Lab @labpuissant.bsky.social · 22/06/2025

Wonderful discussion with @landau.bsky.social visiting us at @institut-leucemie.bsky.social @hopitalsaintlouis.bsky.social in sunny Paris to give an inspiring talk on cutting-edge single-cell technologies. Thank you so much Dan for stopping by and see you soon! @lobrylab.bsky.social

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Reposted by @lobrylab.bsky.social

Fusion Conferences @fusionconf.bsky.social · 15/05/2025

Day 2 of #MyeloidMalignancies25 is underway. We have more exciting talks after lunch & the poster session later this evening 🗣️🍷 Chaired by: Iannis Aifantis & @rosslevinemd.bsky.social

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Reposted by @lobrylab.bsky.social

Alex Puissant Lab @labpuissant.bsky.social · 11/04/2025

Wonderful time with Paolo Gallipoli from the @qmbci.bsky.social visiting us at @institut-leucemie.bsky.social to give a very inspiring seminar on the role of fatty acid metabolism in leukemia. Thank you so much Paolo and see you soon!!! @lobrylab.bsky.social

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Reposted by @lobrylab.bsky.social

Herranz Lab @herranzlab.bsky.social · 21/01/2025

Happy to share our latest findings @bloodneoplasia.bsky.social uncovering an ACLY-MYC feedforward loop in T-ALL, led by @dasilva-diz.bsky.social doi.org/10.1016/j.bn...

doi.org

Redirecting

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