Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones
- 1Myeloma Institute, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States
Abstract
Multiple myeloma (MM) is a genomically complex malignancy of terminally differentiated plasma cells. Here, we have utilized the SCID-rab patient derived xenograft (PDX) model as a platform to expand scarce primary MM samples across disease stages and major cytogenetic subgroups for comprehensive molecular analysis. The model generated abundant CD138+ cells while retaining key genomic, transcriptomic and proteomic features of corresponding patient tumors. Compared with human myeloma cell lines, PDX cells more closely resembled primary MM in proliferative state and expression of therapeutically relevant targets. WGS and single cell WGS showed that PDXs arose from the selection of pre-existing subclones, including clones harboring high-risk alterations and convergent mechanisms of tumor suppressor inactivation. These findings establish SCID-rab PDX models as a platform for multiomic profiling, studies of clonal evolution, and determining therapeutic response in MM.
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BibTeX
@misc{becker2026genomic,
title = {{Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones}},
author = {N. J. Becker and E. Liu and R. Sharma and P. Sudha and S. Ortega Bertran and O. Jaouadi and S. Mondal and N. Luviano Aparicio and M. Affer and K. K. Mangalaparthi and A. Pandey and M. Papadimitriou and B. T. Diamond and D. G. Coffey and A. Pandey and J. Hoffman and G. Hevroni and D. Kazandjian and K. Lee and G. J. Morgan and F. E. Davies and A. Suvannasankha and A. Mikulasova and O. Landgren and R. Abonour and B. A. Walker},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.14.755992},
url = {https://www.biorxiv.org/content/10.64898/2026.10.14.755992v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones
AU - N. J. Becker
AU - E. Liu
AU - R. Sharma
AU - P. Sudha
AU - S. Ortega Bertran
AU - O. Jaouadi
AU - S. Mondal
AU - N. Luviano Aparicio
AU - M. Affer
AU - K. K. Mangalaparthi
AU - A. Pandey
AU - M. Papadimitriou
AU - B. T. Diamond
AU - D. G. Coffey
AU - A. Pandey
AU - J. Hoffman
AU - G. Hevroni
AU - D. Kazandjian
AU - K. Lee
AU - G. J. Morgan
AU - F. E. Davies
AU - A. Suvannasankha
AU - A. Mikulasova
AU - O. Landgren
AU - R. Abonour
AU - B. A. Walker
PY - 2026
DA - 2026/10/14
PB - bioRxiv
DO - 10.64898/2026.10.14.755992
UR - https://www.biorxiv.org/content/10.64898/2026.10.14.755992v1
AB - Multiple myeloma (MM) is a genomically complex malignancy of terminally differentiated plasma cells. Here, we have utilized the SCID-rab patient derived xenograft (PDX) model as a platform to expand scarce primary MM samples across disease stages and major cytogenetic subgroups for comprehensive molecular analysis. The model generated abundant CD138+ cells while retaining key genomic, transcriptomic and proteomic features of corresponding patient tumors. Compared with human myeloma cell lines, PDX cells more closely resembled primary MM in proliferative state and expression of therapeutically relevant targets. WGS and single cell WGS showed that PDXs arose from the selection of pre-existing subclones, including clones harboring high-risk alterations and convergent mechanisms of tumor suppressor inactivation. These findings establish SCID-rab PDX models as a platform for multiomic profiling, studies of clonal evolution, and determining therapeutic response in MM.
ER -