ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3

Our findings highlight the strong effects of ASXL1 variants that supersede cell-type and even disease states. This is the first direct comparison of transcriptomic and methylation profiles driven by pathogenic variants in a chromatin modifier gene in distinct diseases. Similar to RASopathies, in which pathogenic variants in many genes lead to overlapping phenotypes that can be treated by inhibiting a common pathway, our data identifies common pathways for ASXL1 variants that can be targeted for both disease states. Comparative approaches of high-penetrance genetic variants across cell types and disease states can identify targetable pathways to treat multiple diseases. Finally, our work highlights the connections of epigenes, such as ASXL1, to an underlying stem-cell state in both early development and in malignancy.

Authors

Institutions

Publication Details

Journal
BMC Medical Genomics
Published
2024-11-29
DOI
https://doi.org/10.1186/s12920-024-02039-7
Citations
2
Primary Topic
Epigenetics and DNA Methylation
Type
article
Field-Weighted Citation Impact
0.47

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3

Isabella Lin, Andrew C.A. Wan, Leroy Bondhus, Bianca Russell et al.
2 citations
BMC Medical Genomics
Epigenetics and DNA Methylation
0.47
article

ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3

Isabella Lin, Andrew C.A. Wan, Leroy Bondhus, Bianca Russell, Rosanna Weksberg, Zain Awamleh, Valerie A. Arboleda, Angela Wei, Mili Sinvhal
article en
2 citations

Abstract

Our findings highlight the strong effects of ASXL1 variants that supersede cell-type and even disease states. This is the first direct comparison of transcriptomic and methylation profiles driven by pathogenic variants in a chromatin modifier gene in distinct diseases. Similar to RASopathies, in which pathogenic variants in many genes lead to overlapping phenotypes that can be treated by inhibiting a common pathway, our data identifies common pathways for ASXL1 variants that can be targeted for both disease states. Comparative approaches of high-penetrance genetic variants across cell types and disease states can identify targetable pathways to treat multiple diseases. Finally, our work highlights the connections of epigenes, such as ASXL1, to an underlying stem-cell state in both early development and in malignancy.

BMC Medical GenomicsVol. 17(1)
University of California, Los Angeles (US), University of Toronto (CA), UCLA Health (US), Hospital for Sick Children (CA), Center for Human Genetics (US), Institute of Human Genetics (PL)
W. M. Keck Foundation, Epilepsy Research Program of the Ontario Brain Institute, National Institutes of Health, Canadian Institutes of Health Research, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, NIH Office of the Director, National Institute of General Medical Sciences
Good health and well-being
Openalex Percentile: Top 34%
Epigenetics and DNA Methylation
0.47
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.