Accelerated single cell seeding in relapsed multiple myeloma

Landau, Heather J.; Yellapantula, Venkata; Diamond, Benjamin T.; Rustad, Even H.; Maclachlan, Kylee H.; Gundem, Gunes; Medina-Martinez, Juan; Ossa, Juan Arango; Levine, Max F.; Zhou, Yangyu; Kappagantula, Rajya; Baez, Priscilla; Attiyeh, Marc; Makohon-Moore, Alvin; Zhang, Lance; Boyle, Eileen M.; Ashby, Cody; Blaney, Patrick; Patel, Minal; Zhang, Yanming; Dogan, Ahmet; Chung, David J.; Giralt, Sergio; Lahoud, Oscar B.; Peled, Jonathan U.; Scordo, Michael; Shah, Gunjan; Hassoun, Hani; Korde, Neha S.; Lesokhin, Alexander M.; Lu, Sydney; Mailankody, Sham; Shah, Urvi; Smith, Eric; Hultcrantz, Malin L.; Ulaner, Gary A.; Rhee, Frits; Morgan, Gareth J.; Landgren, Ola; Papaemmanuil, Elli; Iacobuzio-Donahue, Christine; Maura, Francesco

Accelerated single cell seeding in relapsed multiple myeloma

Heather J. Landau, Venkata Yellapantula, Benjamin T. Diamond, Even H. Rustad, Kylee H. Maclachlan, Gunes Gundem, Juan Medina-Martinez, Juan Arango Ossa, Max F. Levine, Yangyu Zhou, Rajya Kappagantula, Priscilla Baez, Marc Attiyeh, Alvin Makohon-Moore, Lance Zhang, Eileen M. Boyle, Cody Ashby, Patrick Blaney, Minal Patel, Yanming Zhang, Ahmet Dogan, David J. Chung, Sergio Giralt, Oscar B. Lahoud, Jonathan U. Peled, Michael Scordo, Gunjan Shah, Hani Hassoun, Neha S. Korde, Alexander M. Lesokhin, Sydney Lu, Sham Mailankody, Urvi Shah, Eric Smith, Malin L. Hultcrantz, Gary A. Ulaner, Frits Rhee, Gareth J. Morgan, Ola Landgren, Elli Papaemmanuil, Christine Iacobuzio-Donahue and Francesco Maura ()
Additional contact information
Heather J. Landau: Memorial Sloan Kettering Cancer Center
Venkata Yellapantula: Memorial Sloan Kettering Cancer Center
Benjamin T. Diamond: Memorial Sloan Kettering Cancer Center
Even H. Rustad: Memorial Sloan Kettering Cancer Center
Kylee H. Maclachlan: Memorial Sloan Kettering Cancer Center
Gunes Gundem: Memorial Sloan Kettering Cancer Center
Juan Medina-Martinez: Memorial Sloan Kettering Cancer Center
Juan Arango Ossa: Memorial Sloan Kettering Cancer Center
Max F. Levine: Memorial Sloan Kettering Cancer Center
Yangyu Zhou: Memorial Sloan Kettering Cancer Center
Rajya Kappagantula: Memorial Sloan Kettering Cancer Center
Priscilla Baez: Memorial Sloan Kettering Cancer Center
Marc Attiyeh: Memorial Sloan Kettering Cancer Center
Alvin Makohon-Moore: Memorial Sloan Kettering Cancer Center
Lance Zhang: Memorial Sloan Kettering Cancer Center
Eileen M. Boyle: NYU Perlmutter Cancer Center
Cody Ashby: University of Arkansas for Medical Sciences
Patrick Blaney: NYU Perlmutter Cancer Center
Minal Patel: Memorial Sloan Kettering Cancer Center
Yanming Zhang: Memorial Sloan Kettering Cancer Center
Ahmet Dogan: Memorial Sloan Kettering Cancer Center
David J. Chung: Memorial Sloan Kettering Cancer Center
Sergio Giralt: Memorial Sloan Kettering Cancer Center
Oscar B. Lahoud: Memorial Sloan Kettering Cancer Center
Jonathan U. Peled: Memorial Sloan Kettering Cancer Center
Michael Scordo: Memorial Sloan Kettering Cancer Center
Gunjan Shah: Memorial Sloan Kettering Cancer Center
Hani Hassoun: Weill Cornell Medical College
Neha S. Korde: Weill Cornell Medical College
Alexander M. Lesokhin: Weill Cornell Medical College
Sydney Lu: Weill Cornell Medical College
Sham Mailankody: Weill Cornell Medical College
Urvi Shah: Weill Cornell Medical College
Eric Smith: Weill Cornell Medical College
Malin L. Hultcrantz: Weill Cornell Medical College
Gary A. Ulaner: Memorial Sloan Kettering Cancer Center
Frits Rhee: University of Arkansas for Medical Sciences
Gareth J. Morgan: NYU Perlmutter Cancer Center
Ola Landgren: Weill Cornell Medical College
Elli Papaemmanuil: Memorial Sloan Kettering Cancer Center
Christine Iacobuzio-Donahue: Memorial Sloan Kettering Cancer Center
Francesco Maura: Memorial Sloan Kettering Cancer Center

Nature Communications, 2020, vol. 11, issue 1, 1-10

Abstract: Abstract Multiple myeloma (MM) progression is characterized by the seeding of cancer cells in different anatomic sites. To characterize this evolutionary process, we interrogated, by whole genome sequencing, 25 samples collected at autopsy from 4 patients with relapsed MM and an additional set of 125 whole exomes collected from 51 patients. Mutational signatures analysis showed how cytotoxic agents introduce hundreds of unique mutations in each surviving cancer cell, detectable by bulk sequencing only in cases of clonal expansion of a single cancer cell bearing the mutational signature. Thus, a unique, single-cell genomic barcode can link chemotherapy exposure to a discrete time window in a patient′s life. We leveraged this concept to show that MM systemic seeding is accelerated at relapse and appears to be driven by the survival and subsequent expansion of a single myeloma cell following treatment with high-dose melphalan therapy and autologous stem cell transplant.

Date: 2020
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DOI: 10.1038/s41467-020-17459-z

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