Issues
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Cover Image
Cover Image
The surface of a healthy B lymphocyte is covered with Y-shaped B-cell receptors (BCR), which transmit signals as vital for B-cell survival as sunlight is for trees (left). In this issue, Varano and colleagues shed light on the biology of high-grade B-cell lymphomas with “double-hit” MYC and BCL2 rearrangements (HGBCL-DH), which resemble a germinal center’s dark zone cells and survive without detectable BCR on the surface. HGBCL-DH linger in a dark zone state, reactivating RAG recombinases, which then translocate oncogenes into immunoglobulin light-chain loci in a futile attempt to revise BCR specificity. In this setting, lymphoma cells survive without light (chain) and functional surface BCR, sustained instead by a residual signal (“glow”) of the intracellular immunoglobulin heavy chain. For more information, see article on page 364 and a Spotlight by Shevchenko and Hodson on page 284. - PDF Icon PDF LinkTable of Contents
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In This Issue
News in Depth
In the Spotlight
In Focus
Research Brief
Clinical Significance of TP53-Mutant Clonal Hematopoiesis Across Diseases
A large-scale population study links TP53-mutant clonal hematopoiesis to increased risk of hematologic malignancies and respiratory mortality, with contributions of germline variants, environmental factors, and somatic mutations.
Research Articles
Single-cell Transcriptional Atlas of Human Hematopoiesis Reveals Genetic and Hierarchy-Based Determinants of Aberrant AML Differentiation
Comparing scRNA-seq data of >1 million cells from 318 patients to a reference atlas of >260K normal human bone marrow cells revealed diverse ways in which differentiation can be disrupted in AML.
DNA Methylation Epitypes of Burkitt Lymphoma with Distinct Molecular and Clinical Features
DNA methylation profiling reveals two BL epitypes with distinct molecular and clinical features, offering a new framework for understanding BL pathogenesis.
Enhancer Hijacking Discovery in Acute Myeloid Leukemia by Pyjacker Identifies MNX1 Activation via Deletion 7q
Systematic discovery of enhancer hijacking in complex karyotype acute myeloid leukemia via the new tool Pyjacker identifies MNX1 activation, a novel leukemogenic event that can result from 7q deletion, among other events.
B-cell Receptor Silencing Reveals the Origin and Dependencies of High-Grade B-cell Lymphomas with MYC and BCL2 Rearrangements
Double-hit Myc/Bcl-2 lymphomas lacking surface BCR evolve from BCL2-translocated dark zone–like state via reactivating RAG, followed by MYC translocation into unproductively recombined Ig-lambda locus.
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