The Silence of the Lambdas: Hidden Complexities in the Evolution of Double-Hit Lymphomas

Summary: In this issue of Blood Cancer Discovery, Varano and colleagues uncover a substantial fraction of high-grade B-cell lymphoma with MYC and BCL2(-BCL6) translocations (so called “double-hit” lymphomas or high-grade B-cell lymphoma–double-hit–BCL2) that lack detectable expression of the B-cell receptor. MYC translocation in these cells is mediated by RAG enzymes, induced in response to silencing of the B-cell receptor in a precursor cell, a feature that renders them resistant to polatuzumab vedotin. See related article by Varano et al., p. XX