E2A deficiency leads to abnormalities in alphabeta T-cell development and to rapid development of T-cell lymphomas.
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.
Bain
G
G
Department of Biology, University of California, San Diego, La Jolla 92093, USA.
Engel
I
I
Robanus Maandag
E C
EC
te Riele
H P
HP
Voland
J R
JR
Sharp
L L
LL
Chun
J
J
Huey
B
B
Pinkel
D
D
Murre
C
C
D000818:Animals; D002454:Cell Differentiation; D002457:Cell Extracts; D002467:Cell Nucleus / Q000378:metabolism; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D016131:Lymphocyte Subsets; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000166:cytology*; D051820:TCF Transcription Factors; D013945:Thymoma / Q000235:genetics / Q000276:immunology; D013950:Thymus Gland / Q000254:growth & development / Q000276:immunology*; D013953:Thymus Neoplasms / Q000235:genetics / Q000276:immunology*; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D051820:TCF Transcription Factors; C544912:TCF7L1 protein, human; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors