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A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma.
Pilcher, William C; Yao, Lijun; Gonzalez-Kozlova, Edgar; Pita-Juarez, Yered; Karagkouni, Dimitra; Acharya, Chaitanya R; Michaud, Marina E; Hamilton, Mark; Nanda, Shivani; Song, Yizhe; Sato, Kazuhito; Wang, Julia T; Satpathy, Sarthak; Ma, Yuling; Schulman, Jessica; D'Souza, Darwin; Jayasinghe, Reyka G; Cheloni, Giulia; Bakhtiari, Mojtaba; Pabustan, Nick; Nie, Kai; Foltz, Jennifer A; Saldarriaga, Isabella; Alaaeldin, Rania; Lepisto, Eva; Chen, Rachel; Fiala, Mark A; Thomas, Beena E; Cook, April; Dos Santos, Junia Vieira; Chiang, I-Ling; Figueiredo, Igor; Fortier, Julie; Slade, Michael; Oh, Stephen T; Rettig, Michael P; Anderson, Emilie; Li, Ying; Dasari, Surendra; Strausbauch, Michael A; Simon, Vernadette A; Rahman, Adeeb H; Chen, Zhihong; Lagana, Alessandro; DiPersio, John F; Rosenblatt, Jacalyn; Kim-Schulze, Seunghee; Dhodapkar, Madhav V; Lonial, Sagar; Kumar, Shaji.
  • Pilcher WC; Coultier Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
  • Yao L; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Gonzalez-Kozlova E; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Pita-Juarez Y; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Karagkouni D; Harvard Medical School, Boston, MA, USA.
  • Acharya CR; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Michaud ME; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Hamilton M; Harvard Medical School, Boston, MA, USA.
  • Nanda S; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Song Y; MMRF, Norwalk, CT, USA.
  • Sato K; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
  • Wang JT; MMRF, Norwalk, CT, USA.
  • Satpathy S; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Ma Y; Harvard Medical School, Boston, MA, USA.
  • Schulman J; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • D'Souza D; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Jayasinghe RG; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Cheloni G; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Bakhtiari M; Department of Biomedical Informatics, Emory School of Medicine, Atlanta, GA, USA.
  • Pabustan N; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Nie K; Harvard Medical School, Boston, MA, USA.
  • Foltz JA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Saldarriaga I; MMRF, Norwalk, CT, USA.
  • Alaaeldin R; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Lepisto E; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Chen R; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Fiala MA; Harvard Medical School, Boston, MA, USA.
  • Thomas BE; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
  • Cook A; MMRF, Norwalk, CT, USA.
  • Dos Santos JV; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Chiang IL; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Figueiredo I; Beth Israel Deaconess Medical Center, Boston, MA, USA.
  • Fortier J; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
  • Slade M; MMRF, Norwalk, CT, USA.
  • Oh ST; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rettig MP; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
  • Anderson E; Department of Pediatrics, Emory School of Medicine, Atlanta, GA, USA.
  • Li Y; MMRF, Norwalk, CT, USA.
  • Dasari S; Tisch Cancer Institute, Department of Immunology and Immunotherapy, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Strausbauch MA; Department of Medicine, Washington University in St. Louis, St. Louis, MO, USA.
  • Simon VA; Human Immune Monitoring Center, Tisch Cancer Institute, Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Rahman AH; Bone Marrow Transplantation & Leukemia Section, Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
  • Chen Z; Division of Hematology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
  • Lagana A; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
  • DiPersio JF; Immunomonitoring Laboratory, Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA.
  • Rosenblatt J; Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA.
  • Kim-Schulze S; Mayo Clinic, Rochester, MN, USA.
  • Dhodapkar MV; Mayo Clinic, Rochester, MN, USA.
  • Lonial S; Mayo Clinic, Rochester, MN, USA.
  • Kumar S; Mayo Clinic, Rochester, MN, USA.
bioRxiv ; 2024 May 17.
Article en En | MEDLINE | ID: mdl-38798338
ABSTRACT
Multiple Myeloma (MM) remains incurable despite advances in treatment options. Although tumor subtypes and specific DNA abnormalities are linked to worse prognosis, the impact of immune dysfunction on disease emergence and/or treatment sensitivity remains unclear. We established a harmonized consortium to generate an Immune Atlas of MM aimed at informing disease etiology, risk stratification, and potential therapeutic strategies. We generated a transcriptome profile of 1,149,344 single cells from the bone marrow of 263 newly diagnosed patients enrolled in the CoMMpass study and characterized immune and hematopoietic cell populations. Associating cell abundances and gene expression with disease progression revealed the presence of a proinflammatory immune senescence-associated secretory phenotype in rapidly progressing patients. Furthermore, signaling analyses suggested active intercellular communication involving APRIL-BCMA, potentially promoting tumor growth and survival. Finally, we demonstrate that integrating immune cell levels with genetic information can significantly improve patient stratification.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Idioma: En Año: 2024 Tipo del documento: Article