文章基本信息

标题：Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function
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作者：Honyin Chiu ; Roberta Buono ; Leandra V. Jackson 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：7
页码：1-16
DOI：10.1016/j.isci.2021.102748
语种：English
出版社：Elsevier
摘要：SummaryThe 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 usedEif4egermline and conditional knockout models to assess the impact of reducedEif4egene 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 ofEif4eimpairs transformation and reduces fitness in competition assaysin vitroandin vivo. In contrast, reducedEif4egene 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.Graphical abstractDisplay OmittedHighlights•Loss of one allele ofEif4eimpairs pre-B-cell leukemia transformation•Eif4e+/-leukemia cells had reduced competitive fitness bothin vitroandin vivo•ReducedEif4edosage had no effect on B-cell development, survival, or proliferationMolecular biology; Cell biology; Cancer