Single Cell Phenotypic Profiling of 27 DLBCL Cases Reveals Marked Intertumoral and Intratumoral Heterogeneity. Issue 6 (22nd October 2019)

• Record Type: Journal Article
• Authors: Nissen, Michael D.; Kusakabe, Manabu; Wang, Xuehai; Simkin, Guillermo; Gracias, Deanne; Tyshchenko, Kateryna; Hill, Ainsleigh; Meskas, Justin; Hung, Stacy; Chavez, Elizabeth A.; Ennishi, Daisuke; Aoki, Tomohiro; Sarkozy, Clementine; Connors, Joseph M.; Farinha, Pedro; Slack, Graham W.; Gascoyne, Randy D.; Brinkman, Ryan R.; Scott, David W.; Steidl, Christian; Weng, Andrew P.
• Other Names: Görgens André guestEditor.; Nolan John guestEditor.; Giebel Bernd guestEditor.
• Is Part Of: Cytometry. Volume 97:Issue 6(2020)
• Page Start: 620
• Page End: 629
• Publication Date: 2019-10-22
• Subjects: Mass cytometry -- CyTOF -- flow cytometry -- FACS -- lymphoma -- DLBCL -- cell‐of‐origin -- HLA‐DR -- EZH2 -- lymph node; Flow cytometry -- Periodicals; Imaging systems in biology -- Periodicals; Imaging systems in medicine -- Periodicals; Diagnostic imaging -- Periodicals; 571.605
• DOI: 10.1002/cyto.a.23919
• Languages: English
• ISSNs: 1552-4922

Abstract

Abstract: Diffuse large B‐cell lymphoma (DLBCL) is the most common histologic subtype of non‐Hodgkin lymphoma and is notorious for its clinical heterogeneity. Patient outcomes can be predicted by cell‐of‐origin (COO) classification, demonstrating that the underlying transcriptional signature of malignant B‐cells informs biological behavior in the context of standard combination chemotherapy regimens. In the current study, we used mass cytometry (CyTOF) to examine tumor phenotypes at the protein level with single cell resolution in a collection of 27 diagnostic DLBCL biopsy specimens from treatment naïve patients. We found that malignant B‐cells from each patient occupied unique regions in 37‐dimensional phenotypic space with no apparent clustering of samples into discrete subtypes. Interestingly, variable MHC class II expression was found to be the greatest contributor to phenotypic diversity. Within individual tumors, a subset of cases showed multiple phenotypic subpopulations, and in one case, we were able to demonstrate direct correspondence between protein‐level phenotypic subsets and DNA mutation‐defined subclones. In summary, CyTOF analysis can resolve both intertumoral and intratumoral heterogeneity among primary samples and reveals that each case of DLBCL is unique and may be comprised of multiple, genetically distinct subclones. © 2019 International Society for Advancement of Cytometry