Research ArticleCancer

Targetable genetic alterations of TCF4 (E2-2) drive immunoglobulin expression in diffuse large B cell lymphoma

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Science Translational Medicine  19 Jun 2019:
Vol. 11, Issue 497, eaav5599
DOI: 10.1126/scitranslmed.aav5599

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Lymphoma’s gain is its loss

Activated B cell (ABC-like) diffuse large B cell lymphoma (DLBCL) can be curable, but therapies are needed for those who relapse or are refractory to current treatments. Jain et al. found that a percentage of ABC-like DLBCL patient tumors had copy gains on part of chromosome 18. The gains increased expression of transcription factor TCF4 (E2-2), which, in turn, activated immunoglobulin μ and MYC. Finding that tumors with this gain were dependent on TCF4 and that TCF4 was regulated by bromodomain protein BRD4, they tested bromodomain inhibition in xenograft models and reported reduced tumor growth and enhanced survival. This work suggests that targeting TCF4 may hold promise against ABC-like DLBCL.

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