Research ArticleLEUKEMIA

MAFB enhances oncogenic Notch signaling in T cell acute lymphoblastic leukemia

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Science Signaling  14 Nov 2017:
Vol. 10, Issue 505, eaam6846
DOI: 10.1126/scisignal.aam6846

New targets, better mouse model for leukemia

T cell acute lymphoblastic leukemias (T-ALLs) are often caused by mutations in the gene encoding Notch1, which mediates cell-cell contact signaling in embryonic development and adult tissue maintenance. However, mice expressing these mutants frequently fail to develop T-ALL. Pajcini et al. found that the transcription factors MAFB and ETS2 increased the expression of Notch1 target genes in mouse and human T-ALL cells by recruiting histone acetyltransferases. Expressing MAFB enhanced the development of Notch1-mutant T-ALL in mice. Because Notch1 is critical for the maintenance of various healthy adult tissues, developing a way to inhibit MAFB or its interacting partners may be a more targeted therapy for leukemia patients.

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