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Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma

Author

Listed:
  • Maximilian Merz

    (Roswell Park Comprehensive Cancer Center (Roswell Park)
    University Hospital Leipzig)

  • Almuth Maria Anni Merz

    (Roswell Park Comprehensive Cancer Center (Roswell Park))

  • Jie Wang

    (Roswell Park)

  • Lei Wei

    (Roswell Park)

  • Qiang Hu

    (Roswell Park)

  • Nicholas Hutson

    (Roswell Park)

  • Cherie Rondeau

    (Roswell Park Comprehensive Cancer Center (Roswell Park))

  • Kimberly Celotto

    (Roswell Park Comprehensive Cancer Center (Roswell Park))

  • Ahmed Belal

    (Roswell Park)

  • Ronald Alberico

    (Roswell Park)

  • AnneMarie W. Block

    (Roswell Park)

  • Hemn Mohammadpour

    (Roswell Park)

  • Paul K. Wallace

    (Roswell Park)

  • Joseph Tario

    (Roswell Park)

  • Jesse Luce

    (Roswell Park)

  • Sean T. Glenn

    (Roswell Park)

  • Prashant Singh

    (Roswell Park)

  • Megan M. Herr

    (Roswell Park)

  • Theresa Hahn

    (Roswell Park)

  • Mehmet Samur

    (Dana Farber Cancer Institute
    Harvard T.H. Chan School of Public Health
    Harvard Medical School)

  • Nikhil Munshi

    (Harvard Medical School
    VA Boston Healthcare System)

  • Song Liu

    (Roswell Park)

  • Philip L. McCarthy

    (Roswell Park)

  • Jens Hillengass

    (Roswell Park Comprehensive Cancer Center (Roswell Park))

Abstract

Osteolytic lesions (OL) characterize symptomatic multiple myeloma. The mechanisms of how malignant plasma cells (PC) cause OL in one region while others show no signs of bone destruction despite subtotal infiltration remain unknown. We report on a single-cell RNA sequencing (scRNA-seq) study of PC obtained prospectively from random bone marrow aspirates (BM) and paired imaging-guided biopsies of OL. We analyze 148,630 PC from 24 different locations in 10 patients and observe vast inter- and intra-patient heterogeneity based on scRNA-seq analyses. Beyond the limited evidence for spatial heterogeneity from whole-exome sequencing, we find an additional layer of complexity by integrated analysis of anchored scRNA-seq datasets from the BM and OL. PC from OL are characterized by differentially expressed genes compared to PC from BM, including upregulation of genes associated with myeloma bone disease like DKK1, HGF and TIMP-1 as well as recurrent downregulation of JUN/FOS, DUSP1 and HBB. Assessment of PC from longitudinally collected samples reveals transcriptional changes after induction therapy. Our study contributes to the understanding of destructive myeloma bone disease.

Suggested Citation

  • Maximilian Merz & Almuth Maria Anni Merz & Jie Wang & Lei Wei & Qiang Hu & Nicholas Hutson & Cherie Rondeau & Kimberly Celotto & Ahmed Belal & Ronald Alberico & AnneMarie W. Block & Hemn Mohammadpour , 2022. "Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28266-z
    DOI: 10.1038/s41467-022-28266-z
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    References listed on IDEAS

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    1. Junyue Cao & Malte Spielmann & Xiaojie Qiu & Xingfan Huang & Daniel M. Ibrahim & Andrew J. Hill & Fan Zhang & Stefan Mundlos & Lena Christiansen & Frank J. Steemers & Cole Trapnell & Jay Shendure, 2019. "The single-cell transcriptional landscape of mammalian organogenesis," Nature, Nature, vol. 566(7745), pages 496-502, February.
    2. S. Manier & J. Park & M. Capelletti & M. Bustoros & S. S. Freeman & G. Ha & J. Rhoades & C. J. Liu & D. Huynh & S. C. Reed & G. Gydush & K. Z. Salem & D. Rotem & C. Freymond & A. Yosef & A. Perilla-Gl, 2018. "Whole-exome sequencing of cell-free DNA and circulating tumor cells in multiple myeloma," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    3. Mehmet Kemal Samur & Mariateresa Fulciniti & Anil Aktas Samur & Abdul Hamid Bazarbachi & Yu-Tzu Tai & Rao Prabhala & Alejandro Alonso & Adam S. Sperling & Timothy Campbell & Fabio Petrocca & Kristen H, 2021. "Biallelic loss of BCMA as a resistance mechanism to CAR T cell therapy in a patient with multiple myeloma," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    4. Zhan Yao & Rona Yaeger & Vanessa S. Rodrik-Outmezguine & Anthony Tao & Neilawattie M. Torres & Matthew T. Chang & Matthias Drosten & Huiyong Zhao & Fabiola Cecchi & Todd Hembrough & Judith Michels & H, 2017. "Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS," Nature, Nature, vol. 548(7666), pages 234-238, August.
    5. L. Rasche & S. S. Chavan & O. W. Stephens & P. H. Patel & R. Tytarenko & C. Ashby & M. Bauer & C. Stein & S. Deshpande & C. Wardell & T. Buzder & G. Molnar & M. Zangari & F. Rhee & S. Thanendrarajan &, 2017. "Spatial genomic heterogeneity in multiple myeloma revealed by multi-region sequencing," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
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    Cited by:

    1. Jiawei Zhou & Amber Cipriani & Yutong Liu & Gang Fang & Quefeng Li & Yanguang Cao, 2023. "Mapping lesion-specific response and progression dynamics and inter-organ variability in metastatic colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Lukas John & Alexandra M. Poos & Alexander Brobeil & Carolina Schinke & Stefanie Huhn & Nina Prokoph & Raphael Lutz & Barbara Wagner & Maurizio Zangari & Stephan M. Tirier & Jan-Philipp Mallm & Sabrin, 2023. "Resolving the spatial architecture of myeloma and its microenvironment at the single-cell level," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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