Daichi Inoue

@AbdelWahablab @DaichiInoue_Lab @UOsaka_en @Tomo_Isobe Thanks so much @AbdelWahablab , happy to see our long-term efforts out!

@DaichiInoue5 @DaichiInoue_Lab @UOsaka_en @Tomo_Isobe congratulations Daichi @DaichiInoue5 ! great to see this out!

Our findings rationalize why these patients often do well. NUTM1-r drives transformation but doesn't sustain typical stem cell dormancy. This active state makes LSCs easier to clear with standard therapy. Our results support consideration of treatment de-escalation strategies.

NUTM1 rearrangement in infant leukemia leads to unique transcriptomic and epigenetic landscapes, defining a distinct #leukemia subtype. Read the plenary paper in today's new issue of Blood: ow.ly/NOh450Yzh2G #BloodJournal #PlenaryPaper

Indeed, BRD9-NUTM1 leukemia is highly sensitive to Ara-C treatment in vivo, and we found a significantly lower frequency of leukemic stem cells in the BRD9-NUTM1 model compared with the KMT2A-r model.

We conducted a drug screen of 340 compounds. Strikingly, NUTM1-r cells showed profound sensitivity to chemotherapy (like Ara-C) and nucleic acid synthesis inhibitors. This vulnerability is linked to the leukemia's high dependence on active transcription.

Mechanistically, NUTM1 fusions recruit p300 to create an aberrant chromatin state. This leads to global H3K27 acetylation and the creation of open chromatin regions that co-opt both B-lineage and stemness programs, including posterior Hoxa genes.

Is BRD9-NUTM1 a true driver? Yes. In our in vivo models, expressing a single fusion was sufficient to induce serially-transplantable prepro-B-like leukemia, faithfully recapitulating the human disease phenotype.

Using RNA-seq and Methyl Array, we established that NUTM1-r B-ALL is a discrete entity. It is characterized by a unique transcriptional landscape and global DNA hypomethylation, regardless of the 5' fusion partner (e.g., BRD9, AFF1, or ACIN1)

Unlike the "primitive" signatures of KMT2A-r, NUTM1-r leukemias are characterized by robust B-lymphoid commitment, which is confirmed with the iLS ex vivo system. They exhibit high expression of B-cell regulators like EBF1 and MEF2C and low CD34 expression.

NUTM1-r B-ALL is a significant subset of infant leukemia, specifically in those lacking KMT2A-rearrangements. Despite its clinical importance, the precise molecular mechanisms driving this disease have remained poorly understood—until now.

Excited to share our latest work in @BloodPortfolio "Plenary Paper"! We present a comprehensive molecular and functional map of NUTM1-rearranged (NUTM1-r) leukemia. Why does this subtype show such favorable outcomes compared to KMT2A-r? x.gd/BRszp

Happy to see our News & Views is out! We highlight two landmark papers that demonstrate the potential for therapeutic targeting of FSP1 and #ferroptosis in in vivo cancer models. Beautiful work from @ThalesPapaG, Jessalyn Ubellacker, and colleagues. 🥳 nature.com/articles/s4155…

• Leukemia cells exploit the selenoprotein synthesis pathway to manage oxidative stress and escape ferroptosis. • Elucidating the selenoproteins' hierarchy in normal and malignant hematopoiesis can identify therapeutic targets.

Highlight • Selenoproteins play a pivotal role in a lineage-dependent manner in normal hematopoiesis. • Vulnerability to ferroptosis may contribute to the pathology of aged hematopoiesis and malignant hematopoiesis.

Happy to share our most recent review article, "Emerging Paradigms in Redox Regulation: The Role of Selenoproteins in Normal and Malignant Hematopoiesis" #ExpHem @ISEHSociety sciencedirect.com/science/articl…

@LabPuissant Thank you so much for your great feedback @LabPuissant

@DaichiInoue5 It was a fantastic presentation on an outstanding work! Congratulations!!!

#ASH25 Congratulations on your first ASH oral presentation, Wataru Saika. So proud of you, fantastic talk, and fruitful discussion. As an award winner, expand your knowledge to the world!

@TaylorJ_MD Thanks @TaylorJ_MD so nice to see you there!

@DaichiInoue5 Congratulations to the mentor and mentee! Great job! #ASH25

@DangH_Nguyen Happy to see you in person @DangH_Nguyen and thanks for your feedback!

@DaichiInoue5 Congrats on the great work!!! It was great seeing you at #ASH25 @DaichiInoue5

@StanleyCLee @AbdelWahablab Exactly, it was so nice to see @StanleyCLee and the current members

@DaichiInoue5 @AbdelWahablab It was great to see you again, @DaichiInoue5 !! It brought back memories from the good old days in the @AbdelWahablab!

We had unforgettable dinner the night before #ASH25 opening, talking about six years of each. @AbdelWahablab, it was the luckiest thing for me to be a part of the dedicated team. I missed the old days!