期刊
ISCIENCE
卷 24, 期 7, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.102748
关键词
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资金
- National Institutes of Health [T32 AI 060573, R21-AI099656]
- American Society of Hematology Bridge grant [ASH-5557789]
- UC Irvine Chao Family Comprehensive Cancer Center pilot grant from the 2018 Anti-Cancer Challenge
- Chao Family Comprehensive Cancer Center Transgenic Mouse Facility Shared Resource by the National Cancer Institute of the National Institutes of Health [P30CA062203]
- American Cancer Society [PF-14-212-01-RMC, RP-19-181-01-RMC]
- NIH [R35CA242986]
In this study, using knockout models, it was shown that inhibiting eIF4E could be a potential therapeutic option for pre-B-cell leukemia, while preserving the development and function of normal B cells.
The cap-binding protein eukaryotic initiation factor 4E (eIF4E) promotes translation of mRNAs associated with proliferation and survival and is an attractive target for cancer therapeutics. Here, we used Eif4e germline and conditional knockout models to assess the impact of reduced Eif4e gene dosage on B-cell leukemogenesis compared to effects on normal pre-B and mature B-cell function. Using a BCR-ABL-driven pre-B-cell leukemia model, we find that loss of one allele of Eif4e impairs transformation and reduces fitness in competition assays in vitro and in vivo. In contrast, reduced Eif4e gene dosage had no significant effect on development of pre-B and mature B cells or on survival or proliferation of non-transformed B lineage cells. These results demonstrate that inhibition of eIF4E could be a new therapeutic tool for pre-B-cell leukemia while preserving development and function of normal B cells.
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