Synergy between PI3K signaling and MYC in Burkitt lymphomagenesis.
In Burkitt lymphoma (BL), a germinal center B-cell-derived tumor, the pro-apoptotic properties of c-MYC must be counterbalanced. Predicting that survival signals would be delivered by phosphoinositide-3-kinase (PI3K), a major survival determinant in mature B cells, we indeed found that combining constitutive c-MYC expression and PI3K activity in germinal center B cells of the mouse led to BL-like tumors, which fully phenocopy human BL with regard to histology, surface and other markers, and gene expression profile. The tumors also accumulate tertiary mutational events, some of which are recurrent in the human disease. These results and our finding of recurrent PI3K pathway activation in human BL indicate that deregulated c-MYC and PI3K activity cooperate in BL pathogenesis.
Program of Cellular and Molecular Medicine, Children's Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Sandrine
S
Sander
Dinis P
DP
Calado
Lakshmi
L
Srinivasan
Karl
K
Köchert
Baochun
B
Zhang
Maciej
M
Rosolowski
Scott J
SJ
Rodig
Karlheinz
K
Holzmann
Stephan
S
Stilgenbauer
Reiner
R
Siebert
Lars
L
Bullinger
Klaus
K
Rajewsky
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000473:pathology; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D018858:Germinal Center / Q000201:enzymology / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D016271:Proto-Oncogene Proteins c-myc; D019869:Phosphatidylinositol 3-Kinases