Extremely happy to share that the first paper from our lab is now published! Driven by the very talented PhD student Maria Cadefau, we studied how CEBPA mutations shape transcriptional programs in AML. A thread 🧵👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation - Nature Communications
CEBPA is frequently mutated in acute myeloid leukemia (AML), but the transcriptional impact of the AML-associated isoform remains unclear. Here, the authors show that CEBPA-mutant cells have reduced i...
www.nature.com
April 14, 2025 at 1:33 PM
Extremely happy to share that the first paper from our lab is now published! Driven by the very talented PhD student Maria Cadefau, we studied how CEBPA mutations shape transcriptional programs in AML. A thread 🧵👇
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Excited to share our preprint on #HemeSky: "MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia"! @delwelruud.bsky.social and co-authors! www.biorxiv.org/content/10.1... [1/15]
MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia
Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of acute myeloid leukemia (AML). Direct depletion of MECOM using an endogenous auxin...
www.biorxiv.org
January 6, 2025 at 3:46 PM
Excited to share our preprint on #HemeSky: "MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia"! @delwelruud.bsky.social and co-authors! www.biorxiv.org/content/10.1... [1/15]
Kudos to stellar postdoc Shruthi Subramanian on her recently funded Collins Medical Trust Award on CEBPA-mutant leukemia!!! 🥂
December 4, 2024 at 12:06 AM
Kudos to stellar postdoc Shruthi Subramanian on her recently funded Collins Medical Trust Award on CEBPA-mutant leukemia!!! 🥂
We derived clones with heterozygous deletion of the +42kb CEBPA enhancer and these do not differentiate upon MECOM loss, indicating the +42kb enhancer is required to release the repression imposed by MECOM on CEBPA. [9/15]
January 6, 2025 at 3:46 PM
We derived clones with heterozygous deletion of the +42kb CEBPA enhancer and these do not differentiate upon MECOM loss, indicating the +42kb enhancer is required to release the repression imposed by MECOM on CEBPA. [9/15]
Thyroid Hormone Receptor β drives Alveolar type 2 differentiation to Alveolar Type 1 cell differentiation via KLF2 & CEBPA.
Is this the mechanism for Thyroid Hormone’s anti Pulmonary Fibrosis effect?
Very relevant to #CureIPF
👏🏼 Drs Pan, Yu & team!!
www.nature.com/articles/s41...
Is this the mechanism for Thyroid Hormone’s anti Pulmonary Fibrosis effect?
Very relevant to #CureIPF
👏🏼 Drs Pan, Yu & team!!
www.nature.com/articles/s41...
TRβ activation confers AT2-to-AT1 cell differentiation and anti-fibrosis during lung repair via KLF2 and CEBPA - Nature Communications
Here, Xin Pan and colleagues found that activation of thyroid hormone receptor-β is necessary for alveolar epithelial cell differentiation during lung repair and regeneration, and confirmed a specific...
www.nature.com
November 23, 2024 at 4:31 PM
Thyroid Hormone Receptor β drives Alveolar type 2 differentiation to Alveolar Type 1 cell differentiation via KLF2 & CEBPA.
Is this the mechanism for Thyroid Hormone’s anti Pulmonary Fibrosis effect?
Very relevant to #CureIPF
👏🏼 Drs Pan, Yu & team!!
www.nature.com/articles/s41...
Is this the mechanism for Thyroid Hormone’s anti Pulmonary Fibrosis effect?
Very relevant to #CureIPF
👏🏼 Drs Pan, Yu & team!!
www.nature.com/articles/s41...
Talk by Charles Antony from our group, presenting single molecule imaging data on how CEBPA regulates Pol I activity and rRNA transcription in myeloid cells. Charles is also a recipient of the ASH Abstract Achievement Award. Wonderful collaboration with Mustafa Mir and Santosh Adhikari. #ASH24
December 8, 2024 at 6:25 PM
Talk by Charles Antony from our group, presenting single molecule imaging data on how CEBPA regulates Pol I activity and rRNA transcription in myeloid cells. Charles is also a recipient of the ASH Abstract Achievement Award. Wonderful collaboration with Mustafa Mir and Santosh Adhikari. #ASH24
Recently, @tjflemin.bsky.social from our lab, along with @dpastoors.bsky.social + @delwelruud.bsky.social, showed that MECOM represses pro-differentiation factors in AML, particularly CEBPA. Reexpressing CEBPA can force differentiation of these AMLs: tinyurl.com/4tckppkh, tinyurl.com/yck4hbk9 (6/n)
November 24, 2025 at 2:40 PM
Recently, @tjflemin.bsky.social from our lab, along with @dpastoors.bsky.social + @delwelruud.bsky.social, showed that MECOM represses pro-differentiation factors in AML, particularly CEBPA. Reexpressing CEBPA can force differentiation of these AMLs: tinyurl.com/4tckppkh, tinyurl.com/yck4hbk9 (6/n)
Thanks for the opportunity to present our work at the last day of #EHA2025 🤩 on MECOM as a repressor of CEBPA - also see our recent preprint: www.biorxiv.org/content/10.1... and I very much hope you can stay tuned for the final version soon-ish) #erasmusmcblood #hemesky
June 15, 2025 at 8:34 PM
Thanks for the opportunity to present our work at the last day of #EHA2025 🤩 on MECOM as a repressor of CEBPA - also see our recent preprint: www.biorxiv.org/content/10.1... and I very much hope you can stay tuned for the final version soon-ish) #erasmusmcblood #hemesky
Yeni kan kanseri modeli yeni tedavi yöntemlerinin geliştirilmesini hızlandırabilir.
Miyelodisplastik sendromlarda hastalığın ilerlemesine yol açan bir gendeki mutasyon hücresel keşfedildi.
CEBPA👇
www.birmingham.ac.uk/news/2025/ne...
Miyelodisplastik sendromlarda hastalığın ilerlemesine yol açan bir gendeki mutasyon hücresel keşfedildi.
CEBPA👇
www.birmingham.ac.uk/news/2025/ne...
July 5, 2025 at 11:31 AM
Yeni kan kanseri modeli yeni tedavi yöntemlerinin geliştirilmesini hızlandırabilir.
Miyelodisplastik sendromlarda hastalığın ilerlemesine yol açan bir gendeki mutasyon hücresel keşfedildi.
CEBPA👇
www.birmingham.ac.uk/news/2025/ne...
Miyelodisplastik sendromlarda hastalığın ilerlemesine yol açan bir gendeki mutasyon hücresel keşfedildi.
CEBPA👇
www.birmingham.ac.uk/news/2025/ne...
Direct overexpression of CEBPA cDNA in presence of MECOM in 3q26r-MUTZ3 cells bypasses the MECOM-induced block of myeloid differentiation.[10/15]
January 6, 2025 at 3:46 PM
Direct overexpression of CEBPA cDNA in presence of MECOM in 3q26r-MUTZ3 cells bypasses the MECOM-induced block of myeloid differentiation.[10/15]
❗️🔬 New research from @scuartero.bsky.social's lab reveals that CEBPA mutations in #AML increase resistance to inflammation but make cells more vulnerable to protein-folding stress, opening the door to new treatment strategies.
➡️ www.carrerasresearch.org/en/news/a-co...
➡️ www.carrerasresearch.org/en/news/a-co...
May 5, 2025 at 11:50 AM
❗️🔬 New research from @scuartero.bsky.social's lab reveals that CEBPA mutations in #AML increase resistance to inflammation but make cells more vulnerable to protein-folding stress, opening the door to new treatment strategies.
➡️ www.carrerasresearch.org/en/news/a-co...
➡️ www.carrerasresearch.org/en/news/a-co...
Check it out!! New insights from our department on the role of MECOM and CEBPA in AML
👇👇👇
👇👇👇
Excited to share our preprint on #HemeSky: "MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia"! @delwelruud.bsky.social and co-authors! www.biorxiv.org/content/10.1... [1/15]
MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia
Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of acute myeloid leukemia (AML). Direct depletion of MECOM using an endogenous auxin...
www.biorxiv.org
January 6, 2025 at 4:15 PM
Check it out!! New insights from our department on the role of MECOM and CEBPA in AML
👇👇👇
👇👇👇
How do single transcription factors prevent lineage differentiation?
In this issue of Blood, the second paper of my PhD is published. We show that MECOM, a key HSC TF, maintains stem cell state by preventing change through repression of CEBPA. #hemesky ashpublications.org/blood/articl...
In this issue of Blood, the second paper of my PhD is published. We show that MECOM, a key HSC TF, maintains stem cell state by preventing change through repression of CEBPA. #hemesky ashpublications.org/blood/articl...
January 6, 2026 at 5:13 PM
How do single transcription factors prevent lineage differentiation?
In this issue of Blood, the second paper of my PhD is published. We show that MECOM, a key HSC TF, maintains stem cell state by preventing change through repression of CEBPA. #hemesky ashpublications.org/blood/articl...
In this issue of Blood, the second paper of my PhD is published. We show that MECOM, a key HSC TF, maintains stem cell state by preventing change through repression of CEBPA. #hemesky ashpublications.org/blood/articl...
As part of this paper, we are also releasing a set of new RNA-seq data of a large cohort of patients with 3q26 rearrangements collected over the years, including the classical inv(3)/t(3;3) as well as t(3;x). These patients show reduced expression of CEBPA. [11/15]
January 6, 2025 at 3:46 PM
As part of this paper, we are also releasing a set of new RNA-seq data of a large cohort of patients with 3q26 rearrangements collected over the years, including the classical inv(3)/t(3;3) as well as t(3;x). These patients show reduced expression of CEBPA. [11/15]
Delighted to announce that our paper showing the generation of iPSc from a MDS patient & how CEBPA drives disease progression is finally out in Nature Comms!
A big thanks to everybody involved & the great collaborators that have made it possible!
10.1038/s41467-025-60192-8
A big thanks to everybody involved & the great collaborators that have made it possible!
10.1038/s41467-025-60192-8
July 1, 2025 at 6:32 PM
Delighted to announce that our paper showing the generation of iPSc from a MDS patient & how CEBPA drives disease progression is finally out in Nature Comms!
A big thanks to everybody involved & the great collaborators that have made it possible!
10.1038/s41467-025-60192-8
A big thanks to everybody involved & the great collaborators that have made it possible!
10.1038/s41467-025-60192-8
Congrats @tjflemin.bsky.social, @bloodgenes.bsky.social and coauthors! I feel like preprint directly ties together #HemeSky 's favorite two transcription factors: MECOM and CEBPA. As to why these two: I'm heavily biased as our complementary work will also be on biorxiv soon (monday!!)
Stem cell-like states confer poor outcomes in blood cancer—but what mechanisms drive this and how can they be therapeutically targeted? In our new preprint, we show how a single TF represses one enhancer to maintain a subset of high-risk leukemias: 🧵👇
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
January 3, 2025 at 12:51 PM
Congrats @tjflemin.bsky.social, @bloodgenes.bsky.social and coauthors! I feel like preprint directly ties together #HemeSky 's favorite two transcription factors: MECOM and CEBPA. As to why these two: I'm heavily biased as our complementary work will also be on biorxiv soon (monday!!)
Je rekel Ivo glede svetovnega rekorda: "Sam, čebpa Domen ne bi imel dresa in gat, bi pa ziher podrsal!" In to smrtno resno je to rekel🤭😂🤣
March 30, 2025 at 12:00 PM
Je rekel Ivo glede svetovnega rekorda: "Sam, čebpa Domen ne bi imel dresa in gat, bi pa ziher podrsal!" In to smrtno resno je to rekel🤭😂🤣
A complementary pre-print was also posted from @delwelruud.bsky.social and @dpastoors.bsky.social further highlighting the importance of MECOM's repression of CEBPA in AML!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
MECOM is a master repressor of myeloid differentiation through dose control of CEBPA in acute myeloid leukemia
Enhancer translocations, due to 3q26 rearrangements, drive out-of-context MECOM expression in an aggressive subtype of acute myeloid leukemia (AML). Direct depletion of MECOM using an endogenous auxin...
www.biorxiv.org
January 7, 2025 at 10:23 PM
A complementary pre-print was also posted from @delwelruud.bsky.social and @dpastoors.bsky.social further highlighting the importance of MECOM's repression of CEBPA in AML!
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
CEBPA is a TF that is critical for myeloid development. A set of its target genes are upregulated upon MECOM shRNA k.d.. CEBPA motifs are predicted to gain binding of their TF. In addition, CEBP motifs are enriched in upregulated H3K27ac, RUNX1 and P300 peaks compared to unchanged peaks. [8/15]
January 6, 2025 at 3:46 PM
CEBPA is a TF that is critical for myeloid development. A set of its target genes are upregulated upon MECOM shRNA k.d.. CEBPA motifs are predicted to gain binding of their TF. In addition, CEBP motifs are enriched in upregulated H3K27ac, RUNX1 and P300 peaks compared to unchanged peaks. [8/15]
Our model also enabled investigating immediate changes in gene expression applying SLAM-seq (3hrs). We mostly found upregulated genes upon MECOM depletion. CEBPA was also upregulated when MECOM is eliminated by shRNA k.d. or CRISPR-Cas9 mutations in the translocated GATA2 enhancer. [5/15]
January 6, 2025 at 3:46 PM
Our model also enabled investigating immediate changes in gene expression applying SLAM-seq (3hrs). We mostly found upregulated genes upon MECOM depletion. CEBPA was also upregulated when MECOM is eliminated by shRNA k.d. or CRISPR-Cas9 mutations in the translocated GATA2 enhancer. [5/15]
2) 🔬 Sunday Dec 8: 9:45am: Talk #416: Charles Antony (Research Associate) presents single molecule imaging data showing how CEBPA control RNA Pol I molecular kinetics in myeloid cells.
December 6, 2024 at 7:40 PM
2) 🔬 Sunday Dec 8: 9:45am: Talk #416: Charles Antony (Research Associate) presents single molecule imaging data showing how CEBPA control RNA Pol I molecular kinetics in myeloid cells.
Please come see @tjflemin.bsky.social present on his groundbreaking work at @ash-hematology.bsky.social #ASH24 that reveals a surprisingly simple regulatory logic for high-risk AMLs ... Happening soon in Manchester Grand Hyatt San Diego Seaport Ballrooms ABCD:
ash.confex.com/ash/2024/web...
ash.confex.com/ash/2024/web...
Paper: Targeted Protein Degradation Reveals a Repressive Role of Mecom at the <em>CEBPA</Em> Locus to Prevent Differentiation in High-Risk Acute Myeloid Leukemia
ash.confex.com
December 9, 2024 at 11:06 PM
Please come see @tjflemin.bsky.social present on his groundbreaking work at @ash-hematology.bsky.social #ASH24 that reveals a surprisingly simple regulatory logic for high-risk AMLs ... Happening soon in Manchester Grand Hyatt San Diego Seaport Ballrooms ABCD:
ash.confex.com/ash/2024/web...
ash.confex.com/ash/2024/web...
A major challenge for the near future will be to establish inhibitors that either directly target MECOM or promote differentiation by interfering MECOM mediated CEBPA repression. CEBPA expression will be a valuable read-out for MECOM function. [14/15]
January 6, 2025 at 3:46 PM
A major challenge for the near future will be to establish inhibitors that either directly target MECOM or promote differentiation by interfering MECOM mediated CEBPA repression. CEBPA expression will be a valuable read-out for MECOM function. [14/15]
Overexpression of 4xPLDLS significantly upregulates CEBPA and induces partial differentiation. The effect size is not as big as when MECOM is depleted, suggesting that there are more mechanisms in play causing CEBPA repression by MECOM. [13/15]
January 6, 2025 at 3:46 PM
Overexpression of 4xPLDLS significantly upregulates CEBPA and induces partial differentiation. The effect size is not as big as when MECOM is depleted, suggesting that there are more mechanisms in play causing CEBPA repression by MECOM. [13/15]