Reduced eIF4E function impairs B-cell leukemia without altering normal B-lymphocyte function
Autor: | David A. Fruman, Lee-or Herzog, Davide Ruggero, Roberta Buono, Sharmila Mallya, Crystal S. Conn, Honyin Chiu, Leandra V. Jackson |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Pediatric Cancer
Childhood Leukemia Lymphocyte Science Biology Germline Article Rare Diseases Conditional gene knockout cell biology medicine Genetics molecular biology cancer Pediatric Multidisciplinary EIF4E Cancer Translation (biology) Hematology medicine.disease Cell biology Leukemia medicine.anatomical_structure B-cell leukemia Biotechnology |
Zdroj: | iScience, Vol 24, Iss 7, Pp 102748-(2021) iScience, vol 24, iss 7 iScience |
ISSN: | 2589-0042 |
Popis: | Summary 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. Graphical abstract Highlights • Loss of one allele of Eif4e impairs pre-B-cell leukemia transformation • Eif4e+/- leukemia cells had reduced competitive fitness both in vitro and in vivo • Reduced Eif4e dosage had no effect on B-cell development, survival, or proliferation Molecular biology; Cell biology; Cancer |
Databáze: | OpenAIRE |
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