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Publication : Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function.

First Author  Chiu H Year  2021
Journal  iScience Volume  24
Issue  7 Pages  102748
PubMed ID  34278258 Mgi Jnum  J:309124
Mgi Id  MGI:6756253 Doi  10.1016/j.isci.2021.102748
Citation  Chiu H, et al. (2021) Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function. iScience 24(7):102748
abstractText  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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