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. 1997 Aug;17(8):4782–4791. doi: 10.1128/mcb.17.8.4782

E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas.

G Bain 1, I Engel 1, E C Robanus Maandag 1, H P te Riele 1, J R Voland 1, L L Sharp 1, J Chun 1, B Huey 1, D Pinkel 1, C Murre 1
PMCID: PMC232330  PMID: 9234734

Abstract

The E2A gene products, E12 and E47, are critical for proper early B-cell development and commitment to the B-cell lineage. Here we reveal a new role for E2A in T-lymphocyte development. Loss of E2A activity results in a partial block at the earliest stage of T-lineage development. This early T-cell phenotype precedes the development of a T-cell lymphoma which occurs between 3 and 9 months of age. The thymomas are monoclonal and highly malignant and display a cell surface phenotype similar to that of immature thymocytes. In addition, the thymomas generally express high levels of c-myc. As assayed by comparative genomic hybridization, each of the tumor populations analyzed showed a nonrandom gain of chromosome 15, which contains the c-myc gene. Taken together, the data suggest that the E2A gene products play a role early in thymocyte development that is similar to their function in B-lineage determination. Furthermore, the lack of E2A results in development of T-cell malignancies, and we propose that E2A inactivation is a common feature of a wide variety of human T-cell proliferative disorders, including those involving the E2A heterodimeric partners tal-1 and lyl-1.

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Selected References

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