转录组
髓样
生物
体细胞
造血
遗传学
基因
免疫学
干细胞
基因表达
作者
Maki Sakuma,Piers Blombery,Manja Meggendorfer,Claudia Haferlach,M. Lindauer,Uwe M. Martens,Wolfgang Kern,Torsten Haferlach,Wencke Walter
出处
期刊:Leukemia
[Springer Nature]
日期:2023-02-23
卷期号:37 (5): 1080-1091
被引量:31
标识
DOI:10.1038/s41375-023-01857-5
摘要
UBA1 is an X-linked gene and encodes an ubiquitin-activating enzyme. Three somatic mutations altering the alternative start codon (M41) in UBA1 in hematopoietic precursor cells have recently been described, resulting in a syndrome of severe inflammation, cytopenias, and the presence of intracellular vacuoles in hematopoietic precursors - termed VEXAS syndrome, a predominantly male disease. Here we present a patient with clinical features of VEXAS who harbored two novel somatic variants in UBA1 (I894S and N606I). To better understand the clinical relevance and biological consequences of non-M41 (UBA1non-M41) variants, we analyzed the whole genome and transcriptome data of 4168 patients with hematological malignancies and detected an additional 16 UBA1non-M41 putative somatic variants with a clear sex-bias in patients with myeloid malignancies. Patients diagnosed with myeloid malignancies carrying UBA1non-M41 putative somatic variants either had vacuoles or immunodysregulatory symptoms. Analysis of the transcriptome confirmed neutrophil activation in VEXAS patients compared to healthy controls but did not result in a specific transcriptomic signature of UBA1M41 patients in comparison with MDS patients. In summary, we have described multiple putative novel UBA1non-M41 variants in patients with various hematological malignancies expanding the genomic spectrum of VEXAS syndrome.
科研通智能强力驱动
Strongly Powered by AbleSci AI