Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma
Open accessAbstract
Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.
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Force-directed graph analysis revealed separate clustering of TP53-mutant HSPC in comparison with healthy and MF donor cells, with a high degree of interpatient heterogeneity.
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- Authors
- Ledergor, G., Weiner, A., Zada, M., Wang, S.-Y., Cohen, Y. C., Gatt, M. E., Snir, N., Magen, H., Koren-Michowitz, M., Herzog-Tzarfati, K., Keren-Shaul, H., Bornstein, C., Rotkopf, R., Yofe, I., David, E., Yellapantula, V., Kay, S., Salai, M., Ben Yehuda, D., Nagler, A., Shvidel, L., Orr-Urtreger, A., Halpern, K. B., Itzkovitz, S., Landgren, O., San-Miguel, J., Paiva, B., Keats, J. J., Papaemmanuil, E., Avivi, I., Barbash, G. I., Tanay, A., & Amit, I.
- Affiliations
- Tel Aviv Sourasky Medical Center (IL)
- Weizmann Institute of Science (IL)
- Tel Aviv University (IL)
- Hebrew University of Jerusalem (IL)
- Memorial Sloan Kettering Cancer Center (US)
- Clinica Universidad de Navarra (ES)
- Translational Genomics Research Institute (US)
- Corresponding author
- Amit, Ido
- ORCID
- Ledergor, Guy
- Weiner, Assaf
- Zada, Mor
- Wang, Shuang-Yin
- Cohen, Yael C.
- Gatt, Moshe E.
- Snir, Nimrod
- Magen, Hila
- Bornstein, Chamutal
- Rotkopf, Ron
- Yofe, Ido
- David, Eyal
- Yellapantula, Venkata
- Salai, Moshe
- Nagler, Arnon
- Shvidel, Lev
- Halpern, Keren Bahar
- Itzkovitz, Shalev
- Landgren, Ola
- Paiva, Bruno
- Keats, Jonathan J.
- Papaemmanuil, Elli
- Avivi, Irit
- Barbash, Gabriel I.
- Tanay, Amos
- Amit, Ido
- Venue
- Nature Medicine
- Published
- 2018-12
- Volume
- 24
- Issue
- 12
- Pages
- 1867-1876
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2902162324
- Cited by
- 263
- References
- 11
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 25 · 2023: 34 · 2022: 48 · 2021: 45 · 2020: 36 · 2019: 26
- FWCI
- 19.18
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- multiple myeloma, tumor subclonal structure, smoldering multiple myeloma, minimal residual disease, circulating tumor cells, liquid biopsy, single-cell RNA sequencing, disease progression, interindividual variability, bone marrow disease, personalized treatment
- MeSH terms
- Smoldering Multiple Myeloma, Adult, Aged, Aged, 80 and over, Base Sequence, Female, Humans, Male, Middle Aged, Multiple Myeloma, Gene Expression Regulation, Neoplastic, Neoplasm, Residual, Disease Progression, Genetic Heterogeneity
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