Diffuse large B-cell lymphoma patient-derived xenograft models capture the molecular and biological heterogeneity of the disease.

Blood
Bjoern ChapuyMargaret A Shipp

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease defined by transcriptional classifications, specific signaling and survival pathways, and multiple low-frequency genetic alterations. Preclinical model systems that capture the genetic and functional heterogeneity of DLBCL are urgently needed. Here, we generated and characterized a panel of large B-cell lymphoma (LBCL) patient-derived xenograft (PDX) models, including 8 that reflect the immunophenotypic, transcriptional, genetic, and functional heterogeneity of primary DLBCL and 1 that is a plasmablastic lymphoma. All LBCL PDX models were subjected to whole-transcriptome sequencing to classify cell of origin and consensus clustering classification (CCC) subtypes. Mutations and chromosomal rearrangements were evaluated by whole-exome sequencing with an extended bait set. Six of the 8 DLBCL models were activated B-cell (ABC)-type tumors that exhibited ABC-associated mutations such as MYD88, CD79B, CARD11, and PIM1. The remaining 2 DLBCL models were germinal B-cell type, with characteristic alterations of GNA13, CREBBP, and EZH2, and chromosomal translocations involving IgH and either BCL2 or MYC Only 25% of the DLBCL PDX models harbored inactivating TP53 mutations, ...Continue Reading

References

Nov 5, 1987·The New England Journal of Medicine·L M WeissM L Cleary
Aug 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·George WrightLouis M Staudt
Oct 18, 2003·Blood·Rebecca J GreenwaldGerald V Denis
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jose M PoloAri Melnick
Mar 8, 2008·Science·Georg LenzLouis M Staudt
Nov 29, 2008·The New England Journal of Medicine·G LenzUNKNOWN Lymphoma/Leukemia Molecular Profiling Project
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Apr 16, 2010·The New England Journal of Medicine·Georg Lenz, Louis M Staudt
Jun 25, 2010·Nature Reviews. Cancer·Joerg HeyerLynda Chin
Jul 28, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Christian GisselbrechtNorbert Schmitz
Nov 16, 2010·Cancer Cell·Federico BernalLoren D Walensky
Dec 24, 2010·Nature·Vu N NgoLouis M Staudt
Mar 11, 2011·Nature·Laura PasqualucciRiccardo Dalla-Favera
Jul 29, 2011·Nature·Ryan D MorinMarco A Marra
Aug 2, 2011·Nature Genetics·Laura PasqualucciRiccardo Dalla-Favera
Feb 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jens G LohrTodd R Golub
Apr 12, 2012·Drug Discovery Today·Natalie CookDavid A Tuveson
Apr 18, 2012·Nature Reviews. Clinical Oncology·John J TentlerS Gail Eckhardt
Jan 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jenny ZhangSandeep S Dave
Jan 22, 2013·Nature Genetics·Priscilla K BrastianosRameen Beroukhim
Jan 22, 2013·Blood·Heike HornUNKNOWN German High-Grade Non-Hodgkin Lymphoma Study Group
Feb 12, 2013·Nature Biotechnology·Kristian CibulskisGad Getz
Aug 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yong S ChangTomi K Sawyer

❮ Previous
Next ❯

Citations

Nov 9, 2016·Critical Reviews in Oncology/hematology·Makhdum AhmedMichael Wang
Sep 28, 2018·The Journal of Clinical Investigation·Yuan RenJianguo Tao
Oct 29, 2018·Annals of Hematology·Fang-Tian WuJian-Yong Li
Mar 9, 2019·Current Hematologic Malignancy Reports·Jordan N Noble, Anjali Mishra
Jun 23, 2019·Cells·Takahiko Murayama, Noriko Gotoh
May 14, 2017·Journal of Hematology & Oncology·Yunxin LaiPeng Li
Nov 23, 2019·Leukemia & Lymphoma·Ruth FlümannGero Knittel
Oct 1, 2016·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Santiago Montes-MorenoMiguel A Piris
May 26, 2017·Hematological Oncology·Peter W Kyriakides, Giorgio Inghirami
Jun 9, 2017·Current Opinion in Hematology·Marco Pizzi, Giorgio Inghirami
Mar 30, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Leo ZhangMichael Wang
Sep 6, 2020·Trends in Immunology·Teresa FuertesVirginia G de Yebenes
Apr 17, 2021·Current Protocols·Maria Teresa CacciapuotiGiorgio Inghirami
Jul 3, 2021·Cancers·Natalia Yanguas-CasásMargarita Sánchez-Beato
Aug 31, 2021·Frontiers in Immunology·Stefanie N MeyerLaura Pasqualucci

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Castleman Disease

Castleman disease is a rare disorder that involves an overgrowth of cells in the lymph nodes. Unicentric Castleman disease affects one lymph node, usually in the chest or abdomen. Multicentric Castleman disease affects multiple lymph nodes, commonly located in the neck, collarbone, underarm and groin areas. Discover the latest research on Castleman disease here.

Cancer -Omics

A variety of different high-throughput technologies can be used to identify the complete catalog of changes that characterize the molecular profile of cohorts of tumor samples. Discover the latest insights gained from cancer 'omics' in this feed.

B-Cell Lymphoma

B-cell lymphomas include lymphomas that affect B cells. This subtype of cancer accounts for over 80% of non-Hodgkin lymphomas in the US. Here is the latest research.