Genomic characterization of patient derived xenograft models of multiple myeloma reveals selection of multiple pre-existing high risk clones
Year: 2026
Type: preprint
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. Whole genome sequencing (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 multi-omic profiling, studying clonal evolution, and determining therapeutic response in MM.
Authors: Nathan J. Becker, Enze Liu, Riya Sharma, Parvathi Sudha, Sara Ortega Bertran, Oumaima Jaouadi, Sreejeta Mondal, Nelia Luviano, Maurizio Affer, Kiran K. Mangalaparthi, Akhilesh Pandey, Marios Papadimitriou, Benjamin T. Diamond, David G. Coffey, Abhishek Pandey, James Hoffman, Gil Hevroni, Dickran Kazandjian, Kelvin Lee, Gareth J. Morgan, Faith E. Davies, Attaya Suvannasankha, Aneta Mikulasova, Ola Landgren, Rafat Abonour, Brian A. Walker
Institutions: University of Miami, Sylvester Comprehensive Cancer Center, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Mayo Clinic, NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, Institute of Genetics and Cancer, University of Edinburgh
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: Lilly Endowment
OpenAlex ID: W7222497119