期刊
LEUKEMIA & LYMPHOMA
卷 63, 期 5, 页码 1080-1090出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2021.2015587
关键词
Classical Hodgkin lymphoma; microdissection; BCOR; Polycomb; PRC1
资金
- FEBS Long-Term Fellowship
- Polish Ministry of Science and Higher Education
- Wilhelm Sander Stiftung [2018.101.1]
- DFG [KU1315/10-1, SFB 1074]
- NIH [5R01CA071540]
- Minnesota Masonic Charities
- University of Minnesota Medical School and Office of the Vice President for Research
- NCI [R35 CA220499]
- Chemotherapy Foundation
- Follicular Lymphoma Consortium
- LLS SCOR [7012-16]
- LLS TRP [6572-19]
- American Society of Hematology Scholar Award
- European Union [952304]
Loss of BCOR may play a role in the pathogenesis of cHL and the homeostasis of GC-B cells.
BCOR is a component of a variant Polycomb repressive complex 1 (PRC1.1). PRC1 and PRC2 complexes together constitute a major gene regulatory system critical for appropriate cellular differentiation. The gene is upregulated in germinal center (GC) B cells and mutated in a number of hematologic malignancies. We report BCOR inactivating alterations in 4/7 classic Hodgkin lymphoma (cHL) cell lines, subclonal somatic mutations in Hodgkin and Reed-Sternberg (HRS) cells of 4/10 cHL cases, and deletions in HRS cells of 7/17 primary cHL cases. In mice, conditional loss of Bcor driven by AID-Cre in GC B cells resulted in gene expression changes of 46 genes (>2-fold) including upregulated Lef1 that encodes a transcription factor responsible for establishing T-cell identity and Il9r (interleukin-9 receptor), an important member of the cytokine network in cHL. Our findings suggest a role for BCOR loss in cHL pathogenesis and GC-B cell homeostasis.
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