JMML stem cells aren’t epigenetically “stuck” in a fetal state.
They mature postnatally—yet show striking transcriptional plasticity, with oncofetal reprogramming in high-risk disease, challenging the classic “maturation block” model.
doi.org/10.1158/2643...
#JMML #epigenetics #hematology #cancer
Same mutation ≠ same leukemia.
Wagenblast et al. show:
• fetal HSCs readily transform
• postnatal HSCs become resistant
• fetal programs create targetable vulnerabilities
Ontogeny matters: state-of-origin shapes biology & therapy response.
doi.org/10.1158/2159...
#pediatric #AML #stemcells
New Spotlight in @aacrjournals.bsky.social
#Oncogene × #Ontogeny × #Plasticity shape leukemia biology & therapy response.
Two complementary studies show: mutations alone don’t explain disease behavior—developmental state and cellular plasticity matter.
aacrjournals.org/bloodcancerd...
🩸🧬
EpiSci
You keep us on tenterhooks, what are those exciting discoveries??? 😲
Looking forward to find out more, hopefully some time soon.
😉
Absolutely, we see pronounced fetal signatures in JMML, too:
aacrjournals.org/bloodcancerd...
Unfortunately, LIN28B is not well captured in the scRNA data. However, I remember clusters revealing pronounced b-catenin expression patterns.
Will check this again… maybe we can find shared programs.
Exciting topic! Looking forward to reading this preprint.
Very pleased to share our latest pre-print which showcases the incredible hard work and skill of Dr Okan Sevim.
Our continued exploration of β-catenin's contribution to the post transcriptional landscape of blood cells led us to a LIN28B interaction.
1/7
www.biorxiv.org/content/10.6...
Congratulations, Julius and all Co-Authors!
🚨We have an opening for Data Scientists or Bioinformaticians using machine learning and AI with all kinds of molecular data to support cancer research. 🧬
Permanent position, fantastic team, exciting projects—what more could you ask for?
www.lih.lu/en/job/?valu...
Out in print this week @bloodjournal.bsky.social . Very proud of this collaborative work with Prof Karadimitris @imperialimmuno.bsky.social. Thanks to @cancerresearchuk.org and CwC_UK for funding this work. #InfantALL @paediatrics.ox.ac.uk @imm.ox.ac.uk
Thanks for sharing our study!
#Kinderkrebs
#Leukämie
@dkfz.bsky.social
@nct-heidelberg.bsky.social
Interesting story about the role of #oncofetal RNA-binding proteins in #immune #evasion in #ovarian #cancer.
Epigenetics that matters! Very cool work on hard to hard-to-access cell types . Finally some solid epigenetics examples that should be used in textbooks! Congrats to Mathieu and team @embl.org Rome!
Neue Erkenntnisse zu frühkindlicher Leukämie: Leukämiezellen können Programme aus der fetalen Entwicklung erneut aktivieren. Die Ergebnisse eröffnen neue Angriffspunkte für Diagnostik und Therapie.
www.nct-heidelberg.de/das-nct/news...
@dkfz.bsky.social @mphartmann.bsky.social @dblipka.bsky.social
Thank you so much, Tim!!!
And I agree! Our first experience with Blood Cancer Discovery @aacrjournals.bsky.social was really really great. Very quick, communicative and professional, but also absolutely supportive, proactive, flexible and courteous!
Of course, it’s always a pleasure to talk to you! :)
Thanks, Tim!
I will let him know… ;) unfortunately, he’s not on bluesky.
@simonhaas.bsky.social
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@littleoldmewi.bsky.social
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Changya Chen
Fantastic environment at our host institutes @dkfz.bsky.social & @nct-heidelberg.bsky.social
Thanks to all co-authors of this publication:
Deep gratitude to
my friend and shared first co-author Maximilian Schönung
the last authors @joschkah.bsky.social, Christian Flotho, Christoph Plass, Miriam Erlacher, Matthias Schlesner, and especially @dblipka.bsky.social
Multi-omics integration reveals risk-associated gene expression signatures, identifying CD52 as a potential therapeutic target for high-risk JMML.
Anti-CD52 treatment depletes JMML stem cells and disrupts disease propagation in a JMML PDX model.
RAS-pathway mutations induce fetal-like gene expression programs in a JMML mouse model, suggesting RAS-driven oncofetal reprogramming in murine JMML stem cells.
Fetal HSC signatures are enriched in patients without detectable JMML driver mutations at birth.
JMML stem cells show transcriptional plasticity, hijacking parts of distinct developmental programs, including fetal HSC marker genes, leading to mosaic-like developmental expression programs.
This suggests the reactivation rather than preservation of oncofetal signatures.
The postnatal maturation state of JMML stem cells challenges the universality of the maturation block model in pediatric malignancies.
JMML epitypes are prognostic biomarkers in JMML.
Conservation of such disease-specific epigenetic signatures in HSC-like JMML stem cells and downstream immune cells suggests HSCs or early HSPCs as the cells-of-origin in JMML across JMML epitypes.
Epigenomes encode cell type, developmental state, and disease-specific information.
DNA methylomes of JMML stem cells reveal:
1. HSC-like cell type signatures
2. A postnatal maturation state
3. Disease-specific epitypes
ONLINE FIRST ALERT!
Molecular #Plasticity Results in #Oncofetal #Reprogramming and Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia
aacrjournals.org/bloodcancerd...
@aacrjournals.bsky.social
#childhoodcancer
#epigenetics
#precisiononcology
