NPM1c comes from a tiny frameshift that creates a nuclear export signal in what is normally a nucleolar protein. In earlier work, we portrayed its HOX-activating force as a mischievous gremlin straining to escape the nucleus—an image that captured how disruptive this mutant is.
Happy to share our review at Cell Stem Cell as part of their Hallmarks series. As always, a pleasure to work with friends and colleagues Anne Brunet (@brunetlab.bsky.social) and Peggy Goodell(@goodell-lab.bsky.social).
Hallmarks of stem cell aging: Cell Stem Cell www.cell.com/cell-stem-ce...
Now: NPM1c becomes a nestling contemplating potential destinies—(1) majesty of wild-type NPM1’s eagle-like order (2) a menacing hawk that shatters the nucleus as it sparks C-body formation and unleashes HOX programs - subverting life-giving differentiation to life-taking self-perpetuation
And here’s the twist we uncover in the new work ⬇️: the gremlin’s power was never in the cytoplasm at all. NPM1c must act *in the nucleus* through phase separation, bringing together multiple proteins on chromatin to drive AML... Overturning years of assumptions.
Today's the print release of a #RibackLab and #GoodellLab collaboration— we’re excited to share the visual story behind the science, including the dramatic artwork that inspired how we thought about aberrant function of NPM1c - which occurs in about 1 in 3 adult acute myeloid leukemias (#AML).
New paper from my lab! Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis: rdcu.be/eh1Nb Complementary to new work from Steven Chan & @georgevassiliou.bsky.social as described by @goodell-lab.bsky.social: www.nature.com/articles/d41...
Grateful to our incredible team—scientists, artists, and collaborators—who built this story with us. We hope the science and imagery inspire new ways of seeing how leukemias take shape. @gandhardatar.bsky.social , @sciencyelmira.bsky.social , @drawimpacts.bsky.social , and others!
Original work here ⬇️, led by the inimitable Lorenzo Brunetti and Michael Gundry. This work became foundational in the field.
Even more exciting, we find that other AML drivers—like NUP98 and KMT2A fusions—coerce their own “majestic creatures” into the same C-body nightmare, revealing a shared structural logic behind clinically similar leukemias. See the original thread ⬇️ for more insights.
Brunetti et al. show that specific loss of NPM1c from the cytoplasm leads to downregulation
of HOX genes and differentiation in NPM1 mutant AML. Blocking NPM1c nuclear export
by XPO1 inhibition reduce...
Excited to share our review on Hallmark of Stem Cell Aging! With Tom Rando and Peggy Goodell @goodell-lab.bsky.social!!
www.sciencedirect.com/science/arti...
Jennifer Trowbridge
BrunetLab
Metformin could reduce people’s risk of certain age-associated blood cancers, but more work is needed to identify who is likely to benefit.
