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 Attiye; 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 van Rhee; Gareth J Morgan; Ola Landgren; Elli Papaemmanuil; Christine Iacobuzio-Donahue; Francesco Maura; Carl Ola Landgren

doi:10.1038/s41467-020-17459-z

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Accelerated single cell seeding in relapsed multiple myeloma

Journal article

Open access

Peer reviewed

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, …

Nature communications, Vol.11(1), pp.3617-3617

2020-07-17

DOI: https://doi.org/10.1038/s41467-020-17459-z

PMID: 32680998

Abstract

Antineoplastic Combined Chemotherapy Protocols - administration & dosage

Antineoplastic Combined Chemotherapy Protocols - adverse effects

Cell Survival - drug effects

Cell Survival - genetics

Clonal Evolution - drug effects

Disease Progression

Dose-Response Relationship, Drug

Hematopoietic Stem Cell Transplantation - adverse effects

Humans

Male

Melphalan - administration & dosage

Melphalan - adverse effects

Middle Aged

Multiple Myeloma - diagnostic imaging

Multiple Myeloma - genetics

Multiple Myeloma - pathology

Multiple Myeloma - therapy

Mutation - drug effects

Neoplasm Invasiveness - genetics

Neoplasm Invasiveness - pathology

Neoplasm Recurrence, Local - diagnostic imaging

Neoplasm Recurrence, Local - genetics

Neoplasm Recurrence, Local - pathology

Neoplasm Recurrence, Local - therapy

Positron Emission Tomography Computed Tomography

Single-Cell Analysis

Spatio-Temporal Analysis

Transplantation, Autologous - adverse effects

Whole Genome Sequencing

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.

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.130 Lymphomas; 1.130.617 Multiple Myeloma
Web Of Science research areas: Multidisciplinary Sciences
ESI research areas: Clinical Medicine

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Details

Title: Accelerated single cell seeding in relapsed multiple myeloma
Creators: 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 Attiye - Memorial Sloan Kettering Cancer Center
Alvin Makohon-Moore - Memorial Sloan Kettering Cancer Center
Lance Zhang - Memorial Sloan Kettering Cancer Center
Eileen M Boyle - NYU Langone Health
Cody Ashby - University of Arkansas for Medical Sciences
Patrick Blaney - NYU Langone Health
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 - Memorial Sloan Kettering Cancer Center
Neha S Korde - Memorial Sloan Kettering Cancer Center
Alexander M Lesokhin - Memorial Sloan Kettering Cancer Center
Sydney Lu - Memorial Sloan Kettering Cancer Center
Sham Mailankody - Memorial Sloan Kettering Cancer Center
Urvi Shah - Memorial Sloan Kettering Cancer Center
Eric Smith - Memorial Sloan Kettering Cancer Center
Malin L Hultcrantz - Memorial Sloan Kettering Cancer Center
Gary A Ulaner - Memorial Sloan Kettering Cancer Center
Frits van Rhee - University of Arkansas for Medical Sciences
Gareth J Morgan - NYU Langone Health
Ola Landgren - Memorial Sloan Kettering Cancer Center
Elli Papaemmanuil - Memorial Sloan Kettering Cancer Center
Christine Iacobuzio-Donahue - Memorial Sloan Kettering Cancer Center
Francesco Maura - Memorial Sloan Kettering Cancer Center
Carl Ola Landgren - Miller School of Medicine
Publication Details: Nature communications, Vol.11(1), pp.3617-3617
Grant note: U2C CA233284 / NCI NIH HHS R35 CA220508 / NCI NIH HHS P30 CA008748 / NCI NIH HHS K08 HL143189 / NHLBI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Department of Medicine; UMMG Dept of Medicine - Hematology/Oncology
Language: English
Resource Type: Journal article
PMID: 32680998
Record Identifier: 991031714493202976