Aggressive Lymphoma after CD19 CAR T-Cell Therapy.

The development of a fatal, clonal, autonomously proliferating CD4-CD8- chimeric antigen receptor (CAR)+ peripheral T-cell lymphoma (PTCL) occurred 1 month after a patient received treatment with tisagenlecleucel for relapsed primary central nervous system lymphoma. The PTCL had a clonal T-cell receptor rearrangement, which was already detectable in the apheresis product for CAR T-cell manufacturing and 7 months earlier for autologous transplantation. Somatic and mutations in CD34+ stem cells and their progeny were detected in the PTCL, in the apheresis specimen that was obtained for CAR T-cell production, and in the autotransplant.

Glyoxal as an alternative fixative for single-cell RNA sequencing.

Single-cell RNA sequencing has become an important method to identify cell types, delineate the trajectories of cell differentiation in whole organisms, and understand the heterogeneity in cellular responses. Nevertheless, sample collection and processing remain a severe bottleneck for single-cell RNA sequencing experiments. Cell isolation protocols often lead to significant changes in the transcriptomes of cells, requiring novel methods to preserve cell states.

Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial.

Background: Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult patients with refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL).

Methods: Thirteen patients were treated with escalating doses of CD19-directed CARTs between 1 × 10 and 50 × 10 CARTs/m.

A global genetic interaction network by single-cell imaging and machine learning.

Cellular and organismal phenotypes are controlled by complex gene regulatory networks. However, reference maps of gene function are still scarce across different organisms. Here, we generated synthetic genetic interaction and cell morphology profiles of more than 6,800 genes in cultured Drosophila cells.

Small-molecule SUMO inhibition for biomarker-informed B-cell lymphoma therapy.

Aberrant activity of the SUMOylation pathway has been associated with MYC overexpression and poor prognosis in aggressive B-cell lymphoma (BCL) and other malignancies. Recently developed small-molecule inhibitors of SUMOylation (SUMOi) target the heterodimeric E1 SUMO activation complex (SAE1/UBA2). Here, we report that activated MYC signaling is an actionable molecular vulnerability in vitro and in a preclinical murine in vivo model of MYC-driven BCL.

Analysis of Single-Cell Transcriptome Data in Drosophila.

The fly Drosophila is a versatile model organism that has led to fascinating biological discoveries. In the past few years, Drosophila researchers have used single-cell RNA-sequencing (scRNA-seq) to gain insights into the cellular composition, and developmental processes of various tissues and organs. Given the success of single-cell technologies a variety of computational tools and software packages were developed to enable and facilitate the analysis of scRNA-seq data.

Activated SUMOylation restricts MHC class I antigen presentation to confer immune evasion in cancer.

Activated SUMOylation is a hallmark of cancer. Starting from a targeted screening for SUMO-regulated immune evasion mechanisms, we identified an evolutionarily conserved function of activated SUMOylation, which attenuated the immunogenicity of tumor cells. Activated SUMOylation allowed cancer cells to evade CD8+ T cell-mediated immunosurveillance by suppressing the MHC class I (MHC-I) antigen-processing and presentation machinery (APM).

Androglobin gene expression patterns and FOXJ1-dependent regulation indicate its functional association with ciliogenesis.

Androglobin (ADGB) represents the latest addition to the globin superfamily in metazoans. The chimeric protein comprises a calpain domain and a unique circularly permutated globin domain. ADGB expression levels are most abundant in mammalian testis, but its cell-type-specific expression, regulation, and function have remained unexplored.