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Dissecting intratumor heterogeneity of nodal B cell lymphoma on the transcriptional, genetic, and drug response level

Tumor heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is well-known to affect the efficacy of anti-cancer, most personalized treatment approaches do not account for intratumor heterogeneity. We addressed this issue by studying the heterogeneity of lymph node-derived B cell non-Hodgkin lymphoma (B-NHL) by single cell RNA-sequencing (scRNA-seq) and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subclones and compared their drug response and genomic profiles. Malignant subclones of the same patient responded strikingly different to anti-cancer drugs ex vivo, which recapitulated subclone-specific drug sensitivity during in vivo treatment. Tumor infiltrating T cells represented the majority of non-malignant cells, whose gene expression signatures were similar across all donors, whereas the frequencies of T cell subsets varied significantly between the donors. Our data provide new insights into the heterogeneity of B-NHL and highlight the relevance of intratumor heterogeneity for personalized cancer therapies.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006057 HiSeq X Ten 2
EGAD00001006058 HiSeq X Ten 2
EGAD00001006059 Illumina HiSeq 4000 5
EGAD00001006060 Illumina HiSeq 4000 1
Publications Citations
Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.
Nat Cell Biol 25: 2023 481-492