Fu et al. identify biallelic germline ASXL1 variants as the cause of a novel #InbornErrorOfImmunity, linking ASXL1 deficiency to epigenetic dysregulation, combined immune deficiency, chronic viral infections, & malignancy
rupress.org/jem/article/...
rupress.org/jem/article/...
July 31, 2025 at 4:11 PM
Fu et al. identify biallelic germline ASXL1 variants as the cause of a novel #InbornErrorOfImmunity, linking ASXL1 deficiency to epigenetic dysregulation, combined immune deficiency, chronic viral infections, & malignancy
rupress.org/jem/article/...
rupress.org/jem/article/...
- hochsensitive KIT-D816V-Testung (ASO-qPCR oder ddPCR)
- Bei Negativität: NGS des gesamten KIT-Gens für alternative Mutationen
- Myeloid-Mutationspanel (SRSF2, ASXL1, RUNX1 etc.) zur Risikostratifizierung.
4/5
- Bei Negativität: NGS des gesamten KIT-Gens für alternative Mutationen
- Myeloid-Mutationspanel (SRSF2, ASXL1, RUNX1 etc.) zur Risikostratifizierung.
4/5
May 19, 2026 at 7:45 AM
- hochsensitive KIT-D816V-Testung (ASO-qPCR oder ddPCR)
- Bei Negativität: NGS des gesamten KIT-Gens für alternative Mutationen
- Myeloid-Mutationspanel (SRSF2, ASXL1, RUNX1 etc.) zur Risikostratifizierung.
4/5
- Bei Negativität: NGS des gesamten KIT-Gens für alternative Mutationen
- Myeloid-Mutationspanel (SRSF2, ASXL1, RUNX1 etc.) zur Risikostratifizierung.
4/5
I'm reading an interesting perspective on how to "re-activate exhausted T cells" to improve responses to immune checkpoint blockade. They discuss a paper that identifies 3 epigenetic regulators that normally inhibit this therapy. 1/2 🧪
pubmed.ncbi.nlm.nih.gov/39388579/
pubmed.ncbi.nlm.nih.gov/39388579/
November 27, 2024 at 11:00 PM
I'm reading an interesting perspective on how to "re-activate exhausted T cells" to improve responses to immune checkpoint blockade. They discuss a paper that identifies 3 epigenetic regulators that normally inhibit this therapy. 1/2 🧪
pubmed.ncbi.nlm.nih.gov/39388579/
pubmed.ncbi.nlm.nih.gov/39388579/
Preprint alert! 🚨
We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1.
This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6
www.biorxiv.org/content/10.6...
We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1.
This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6
www.biorxiv.org/content/10.6...
Divergent Pathogenic PR-DUB Complex Variants Converge Functionally Via PRC2 Displacement From Chromatin
The PR-DUB complex is responsible for erasing the repressive histone modification, H2AK119ub1. ASXL1-3 proteins are mutually exclusive catalytic partners of BAP1 in the PR-DUB complex. Somatic heteroz...
www.biorxiv.org
July 27, 2026 at 11:30 AM
Preprint alert! 🚨
We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1.
This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6
www.biorxiv.org/content/10.6...
We are very excited to share our new manuscript on Bohring-Opitz syndrome, a devastating rare monogenic disorder driven by truncating variants in ASXL1.
This project was led by PhD student Emma Doyle, one of the OG Conway lab members 💪. 1/6
www.biorxiv.org/content/10.6...
A new paper from @luciedarmusey.bsky.social out this week in Blood Advances! Dr. Darmusey investigated how mutations in ASXL1--often associated with dysplasia--also drive myeloproliferative neoplasms, which are characterized by overproduction of mature cells.
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
Dual ASXL1 and CSF3R mutations drive myeloid-biased stem cell expansion and enhance neutrophil differentiation
Mutations in the epigenetic regulator Additional Sex Combs-Like 1 (ASXL1) are frequently observed in chronic neutrophilic leukemia (CNL). CNL is a mye…
www.sciencedirect.com
April 1, 2025 at 9:54 PM
A new paper from @luciedarmusey.bsky.social out this week in Blood Advances! Dr. Darmusey investigated how mutations in ASXL1--often associated with dysplasia--also drive myeloproliferative neoplasms, which are characterized by overproduction of mature cells.
www.sciencedirect.com/science/arti...
www.sciencedirect.com/science/arti...
ASXL1 deficiency causes epigenetic dysfunction, combined immunodeficiency, and EBV-associated lymphoma @jem.org @turveylab.bsky.social
rupress.org/jem/article/...
rupress.org/jem/article/...
July 31, 2025 at 6:23 PM
ASXL1 deficiency causes epigenetic dysfunction, combined immunodeficiency, and EBV-associated lymphoma @jem.org @turveylab.bsky.social
rupress.org/jem/article/...
rupress.org/jem/article/...
Ubiquitin acts as a proteinaceous glue to fasten the intersubunit interaction within the Polycomb repressive deubiquitinase complex to allosterically enhance its activity
www.nature.com/articles/s41...
www.nature.com/articles/s41...
January 13, 2026 at 8:47 PM
Ubiquitin acts as a proteinaceous glue to fasten the intersubunit interaction within the Polycomb repressive deubiquitinase complex to allosterically enhance its activity
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Moreover, we show in experimental models that reducing MSI2 levels protects human HSCs from phenotypic expansion in ASXL1-mutant CH, whilst MSI2 overexpression cooperates with Asxl1-/- in mouse models to induce myelodysplastic syndrome. (11/n)
March 27, 2025 at 8:31 PM
Moreover, we show in experimental models that reducing MSI2 levels protects human HSCs from phenotypic expansion in ASXL1-mutant CH, whilst MSI2 overexpression cooperates with Asxl1-/- in mouse models to induce myelodysplastic syndrome. (11/n)
Amazing talk from Fernanda Gutierrez-Rodrigues showing our lab’s work on #ClonalHematopoiesis over 10+ years after IST. We saw long-term clonal persistence of ASXL1 and PIGA. #ASH24 @ash-hematology.bsky.social
December 7, 2024 at 6:40 PM
Amazing talk from Fernanda Gutierrez-Rodrigues showing our lab’s work on #ClonalHematopoiesis over 10+ years after IST. We saw long-term clonal persistence of ASXL1 and PIGA. #ASH24 @ash-hematology.bsky.social
ICYMI: "Epigenetic Regulation of T-Cell Differentiation Mediates Immunotherapy Response," a #ResearchWatch summary of recent findings from Tae Gun Kang, Ben Youngblood, Caitlin Zebley, and colleagues.
doi.org/10.1158/2159...
doi.org/10.1158/2159...
Epigenetic Regulation of T-Cell Differentiation Mediates Immunotherapy Response
Major Finding: ASXL1 regulates T-cell terminal differentiation and exhaustion during chronic antigen exposure.Concept: Disruption of ASXL1 alters histone ubiquitination to promote a stem-like effector...
doi.org
November 27, 2024 at 2:48 PM
ICYMI: "Epigenetic Regulation of T-Cell Differentiation Mediates Immunotherapy Response," a #ResearchWatch summary of recent findings from Tae Gun Kang, Ben Youngblood, Caitlin Zebley, and colleagues.
doi.org/10.1158/2159...
doi.org/10.1158/2159...
a study in @bloodjournals.hematology.org illustrating that ASXL1 mutations in CML are a bad actor!
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
September 16, 2025 at 4:54 PM
a study in @bloodjournals.hematology.org illustrating that ASXL1 mutations in CML are a bad actor!
ashpublications.org/blood/articl...
ashpublications.org/blood/articl...
This paper marks our trilogy on H2AK119Ub mechanisms. We have now characterized: PRC1 (the Writer), BAP1/ASXL1 (the Eraser) and DNMT3A1 (the Reader) of H2AK119Ub in collaboration with the amazing labs of Chao Lu, JP Armache, Diego Pasini, Mike Keogh and the Epicypher and Evgeny Nudler.
November 16, 2024 at 5:42 PM
This paper marks our trilogy on H2AK119Ub mechanisms. We have now characterized: PRC1 (the Writer), BAP1/ASXL1 (the Eraser) and DNMT3A1 (the Reader) of H2AK119Ub in collaboration with the amazing labs of Chao Lu, JP Armache, Diego Pasini, Mike Keogh and the Epicypher and Evgeny Nudler.
What I'm wondering is what an immunologist thinks when they read that one of the epigenetic regulators is called additional sex comb-like 1 (Asxl1)? Do they stop for a moment & ask why? Perhaps thank fruit fly biologists of the 1900s for discovering many of these by looking carefully at fly legs 2/2
November 27, 2024 at 11:11 PM
What I'm wondering is what an immunologist thinks when they read that one of the epigenetic regulators is called additional sex comb-like 1 (Asxl1)? Do they stop for a moment & ask why? Perhaps thank fruit fly biologists of the 1900s for discovering many of these by looking carefully at fly legs 2/2
Very proud of this new paper describing a novel human immune defect caused by ASXL1 deficiency.
We really had to open the genomics tool box to solve this one, including neat tricks like calculating the epigenetic age.
All led by Dr. Catherine Biggs!
We really had to open the genomics tool box to solve this one, including neat tricks like calculating the epigenetic age.
All led by Dr. Catherine Biggs!
Fu et al. identify biallelic germline ASXL1 variants as the cause of a novel #InbornErrorOfImmunity, linking ASXL1 deficiency to epigenetic dysregulation, combined immune deficiency, chronic viral infections, & malignancy
rupress.org/jem/article/...
rupress.org/jem/article/...
August 3, 2025 at 11:14 PM
Very proud of this new paper describing a novel human immune defect caused by ASXL1 deficiency.
We really had to open the genomics tool box to solve this one, including neat tricks like calculating the epigenetic age.
All led by Dr. Catherine Biggs!
We really had to open the genomics tool box to solve this one, including neat tricks like calculating the epigenetic age.
All led by Dr. Catherine Biggs!
Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4 www.nature.com/articles/s4...
February 17, 2026 at 3:15 PM
Recruitment of BRD4 to the ASXL1 genomic targets depends on the extra-terminal domain of BRD4 www.nature.com/articles/s4...
Asxl1 truncation promotes the expansion of myeloid-biased stem cells. Adding a Csf3rT621I mutation expands the granulocyte progenitor pool. buff.ly/eGnQT3h #hemesky #myeloidneoplasia
April 18, 2025 at 3:04 PM
Asxl1 truncation promotes the expansion of myeloid-biased stem cells. Adding a Csf3rT621I mutation expands the granulocyte progenitor pool. buff.ly/eGnQT3h #hemesky #myeloidneoplasia
Dr. Zeidner @unchemeonc Lead investigator for Revumenib P2, FDA Approval on to the next #AML success. SLS009 ASXL1+ R/R AML
100% CR Rates
x.com/leukdocjz/st...
100% CR Rates
x.com/leukdocjz/st...
x.com
x.com
December 9, 2024 at 4:19 AM
Dr. Zeidner @unchemeonc Lead investigator for Revumenib P2, FDA Approval on to the next #AML success. SLS009 ASXL1+ R/R AML
100% CR Rates
x.com/leukdocjz/st...
100% CR Rates
x.com/leukdocjz/st...
ASXL1 deficiency causes epigenetic dysfunction, combined #immunodeficiency, and EBV-associated lymphoma, say Maggie Fu, Mehul Sharma, Michael Kobor, Stuart Turvey, Catherine Biggs et al.
rupress.org/jem/article/...
#InbornErrorsOfImmunity
@turveylab.bsky.social
rupress.org/jem/article/...
#InbornErrorsOfImmunity
@turveylab.bsky.social
August 7, 2025 at 7:45 PM
ASXL1 deficiency causes epigenetic dysfunction, combined #immunodeficiency, and EBV-associated lymphoma, say Maggie Fu, Mehul Sharma, Michael Kobor, Stuart Turvey, Catherine Biggs et al.
rupress.org/jem/article/...
#InbornErrorsOfImmunity
@turveylab.bsky.social
rupress.org/jem/article/...
#InbornErrorsOfImmunity
@turveylab.bsky.social
🩺💡Today’s clinical questions!
Swipe to see the answers and explanations!
#CMML #Hematology #HemOnc #Cytokines #MedEd #ChronicMyelomonocyticLeukemia #KRAS #TET2 #SRSF2 #ASXL1 #RUNX1 #Inflammation #NLRP3 #BoneMarrowTransplant #HCT #Oncology #BloodDisorders #HEMEHUB
Swipe to see the answers and explanations!
#CMML #Hematology #HemOnc #Cytokines #MedEd #ChronicMyelomonocyticLeukemia #KRAS #TET2 #SRSF2 #ASXL1 #RUNX1 #Inflammation #NLRP3 #BoneMarrowTransplant #HCT #Oncology #BloodDisorders #HEMEHUB
April 20, 2026 at 10:17 PM
🩺💡Today’s clinical questions!
Swipe to see the answers and explanations!
#CMML #Hematology #HemOnc #Cytokines #MedEd #ChronicMyelomonocyticLeukemia #KRAS #TET2 #SRSF2 #ASXL1 #RUNX1 #Inflammation #NLRP3 #BoneMarrowTransplant #HCT #Oncology #BloodDisorders #HEMEHUB
Swipe to see the answers and explanations!
#CMML #Hematology #HemOnc #Cytokines #MedEd #ChronicMyelomonocyticLeukemia #KRAS #TET2 #SRSF2 #ASXL1 #RUNX1 #Inflammation #NLRP3 #BoneMarrowTransplant #HCT #Oncology #BloodDisorders #HEMEHUB
2/12
CHIP = clonal hematopoiesis of indeterminate potential.
Somatic mutations arise in hematopoietic stem cells and expand in blood, without overt leukemia/MDS.
Common genes: DNMT3A, TET2, ASXL1, JAK2, TP53, PPM1D, SF3B1, SRSF2.
CHIP = clonal hematopoiesis of indeterminate potential.
Somatic mutations arise in hematopoietic stem cells and expand in blood, without overt leukemia/MDS.
Common genes: DNMT3A, TET2, ASXL1, JAK2, TP53, PPM1D, SF3B1, SRSF2.
January 31, 2026 at 2:45 PM
2/12
CHIP = clonal hematopoiesis of indeterminate potential.
Somatic mutations arise in hematopoietic stem cells and expand in blood, without overt leukemia/MDS.
Common genes: DNMT3A, TET2, ASXL1, JAK2, TP53, PPM1D, SF3B1, SRSF2.
CHIP = clonal hematopoiesis of indeterminate potential.
Somatic mutations arise in hematopoietic stem cells and expand in blood, without overt leukemia/MDS.
Common genes: DNMT3A, TET2, ASXL1, JAK2, TP53, PPM1D, SF3B1, SRSF2.
More than you can imagine - Bohring-Opitz Syndrome/ASXL1.
#rarediseaseday #rdd2025 #bohringopitz #bosaware
#rarediseaseday #rdd2025 #bohringopitz #bosaware
February 28, 2025 at 8:41 AM
More than you can imagine - Bohring-Opitz Syndrome/ASXL1.
#rarediseaseday #rdd2025 #bohringopitz #bosaware
#rarediseaseday #rdd2025 #bohringopitz #bosaware
New in @jem.org: Fu et al. identify biallelic germline ASXL1 variants as the cause of a novel #InbornErrorOfImmunity, linking ASXL1 deficiency to epigenetic dysregulation, combined immune deficiency, chronic viral infections, & malignancy
rupress.org/jem/article/...
rupress.org/jem/article/...
July 31, 2025 at 4:45 PM
New in @jem.org: Fu et al. identify biallelic germline ASXL1 variants as the cause of a novel #InbornErrorOfImmunity, linking ASXL1 deficiency to epigenetic dysregulation, combined immune deficiency, chronic viral infections, & malignancy
rupress.org/jem/article/...
rupress.org/jem/article/...
Using an isogenic endogenous model system we have defined the moderate gain-of-function for PR-DUB activity in ASXL1 BOS cells 🧫.
This is driven by a major stabilisation of the truncated ASXL1 protein causing a shift in stoichiometry of PR-DUB complexes toward ASXL1, away from ASXL2. ⚖️ 2/6
This is driven by a major stabilisation of the truncated ASXL1 protein causing a shift in stoichiometry of PR-DUB complexes toward ASXL1, away from ASXL2. ⚖️ 2/6
July 27, 2026 at 11:30 AM
Using an isogenic endogenous model system we have defined the moderate gain-of-function for PR-DUB activity in ASXL1 BOS cells 🧫.
This is driven by a major stabilisation of the truncated ASXL1 protein causing a shift in stoichiometry of PR-DUB complexes toward ASXL1, away from ASXL2. ⚖️ 2/6
This is driven by a major stabilisation of the truncated ASXL1 protein causing a shift in stoichiometry of PR-DUB complexes toward ASXL1, away from ASXL2. ⚖️ 2/6
ASXL1 truncating mutations drive leukemic resistance to T cell attack https://www.biorxiv.org/content/10.1101/2025.05.29.656798v1
June 2, 2025 at 2:50 AM
ASXL1 truncating mutations drive leukemic resistance to T cell attack https://www.biorxiv.org/content/10.1101/2025.05.29.656798v1