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Molecular role of the PAX 5‐ ETV 6 oncoprotein in promoting B‐cell acute lymphoblastic leukemia
Author(s) -
Smeenk Leonie,
Fischer Maria,
Jurado Sabine,
Jaritz Markus,
Azaryan Anna,
Werner Barbara,
Roth Mareike,
Zuber Johannes,
Stanulla Martin,
Boer Monique L,
Mullighan Charles G,
Strehl Sabine,
Busslinger Meinrad
Publication year - 2017
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201695495
Subject(s) - molecular pathology , library science , erasmus+ , humanities , history , art history , biology , art , genetics , gene , the renaissance , computer science
PAX 5 is a tumor suppressor in B‐ ALL , while the role of PAX 5 fusion proteins in B‐ ALL development is largely unknown. Here, we studied the function of PAX 5‐ ETV 6 and PAX 5‐ FOXP 1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested B‐lymphopoiesis at the pro‐B to pre‐B‐cell transition and, contrary to their proposed dominant‐negative role, did not interfere with the expression of most regulated Pax5 target genes. Pax5‐Etv6, but not Pax5‐Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressors in promoting B‐ ALL development. Regulated Pax5‐Etv6 target genes identified in these B‐ ALL s encode proteins implicated in pre‐B‐cell receptor ( BCR ) signaling and migration/adhesion, which could contribute to the proliferation, survival, and tissue infiltration of leukemic B cells. Together with similar observations made in human PAX 5‐ ETV 6 + B‐ ALL s, these data identified PAX 5‐ ETV 6 as a potent oncoprotein that drives B‐cell leukemia development.