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Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.
Zhang, Shaojun; Jiang, Vivian Changying; Han, Guangchun; Hao, Dapeng; Lian, Junwei; Liu, Yang; Zhang, Rongjia; McIntosh, Joseph; Wang, Ruiping; Dang, Minghao; Dai, Enyu; Wang, Yuanxin; Santos, David; Badillo, Maria; Leeming, Angela; Chen, Zhihong; Hartig, Kimberly; Bigcal, John; Zhou, Jia; Kanagal-Shamanna, Rashmi; Ok, Chi Young; Lee, Hun; Steiner, Raphael E; Zhang, Jianhua; Song, Xingzhi; Nair, Ranjit; Ahmed, Sairah; Rodriquez, Alma; Thirumurthi, Selvi; Jain, Preetesh; Wagner-Bartak, Nicolaus; Hill, Holly; Nomie, Krystle; Flowers, Christopher; Futreal, Andrew; Wang, Linghua; Wang, Michael.
Afiliación
  • Zhang S; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Jiang VC; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Han G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hao D; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lian J; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Liu Y; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhang R; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • McIntosh J; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang R; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Dang M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Dai E; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang Y; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Santos D; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Badillo M; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Leeming A; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Chen Z; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hartig K; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Bigcal J; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhou J; Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA.
  • Kanagal-Shamanna R; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ok CY; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Lee H; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Steiner RE; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Zhang J; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Song X; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Nair R; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Ahmed S; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Rodriquez A; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Thirumurthi S; Department of Gastroenterology, Hepathology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Jain P; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wagner-Bartak N; Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Hill H; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Nomie K; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Flowers C; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Futreal A; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
  • Wang L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. lwang22@mdanderson.org.
  • Wang M; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. lwang22@mdanderson.org.
Nat Commun ; 12(1): 2877, 2021 05 17.
Article en En | MEDLINE | ID: mdl-34001881
ABSTRACT
The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Heterogeneidad Genética / Resistencia a Antineoplásicos / Linfoma de Células del Manto / Perfilación de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Heterogeneidad Genética / Resistencia a Antineoplásicos / Linfoma de Células del Manto / Perfilación de la Expresión Génica / Análisis de la Célula Individual / Microambiente Tumoral Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos