Burkitt lymphoma in the mouse.
Chromosomal translocations juxtaposing the MYC protooncogene with regulatory sequences of immunoglobulin (Ig) H chain or kappa (Ig kappa) or lambda (Ig lambda) L chain genes and effecting deregulated expression of MYC are the hallmarks of human Burkitt lymphoma (BL). Here we report that lymphomas with striking similarities to BL develop in mice bearing a mutated human MYC gene controlled by a reconstructed Ig lambda locus encompassing all the elements required for establishment of locus control in vitro. Diffusely infiltrating lymphomas with a typical starry sky appearance occurred in multiple founders and an established line, indicating independence from positional effects. Monoclonal IgM(+)CD5(-)CD23(-) tumors developed from an initially polyclonal population of B cells. These results demonstrate that the phenotype of B lineage lymphomas induced by MYC dysregulation is highly dependent on cooperativity among the regulatory elements that govern expression of the protooncogene and provide a new system for studying the pathogenesis of BL.
Kovalchuk
A L
AL
Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Qi
C F
CF
Torrey
T A
TA
Taddesse-Heath
L
L
Feigenbaum
L
L
Park
S S
SS
Gerbitz
A
A
Klobeck
G
G
Hoertnagel
K
K
Polack
A
A
Bornkamm
G W
GW
Janz
S
S
Morse
H C
HC
D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005091:Exons; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000473:pathology
D016271:Proto-Oncogene Proteins c-myc