Posted: Friday, September 1, 2023
The single-cell protein atlas of multiple myeloma tumors has been revealed and may provide clinicians with information related to tumor behavior and patient outcomes, according to an article published in Blood Cancer Journal. “Recent studies using single-cell RNA sequencing have provided transcriptomic characterization of [multiple myeloma] tumor heterogeneity, but protein-level characterization has not been well reported,” said author Linda B. Baughn, PhD, of the Mayo Clinic, Rochester, Minnesota, and colleagues. “Since most modern therapies target protein pathways, understanding proteomic heterogeneity may provide an opportunity for novel protein-based therapeutic interventions.”
The retrospective study used 49 primary tumor samples from patients with relapsed or refractory multiple myeloma. The investigators used 34 antibody targets directed at both cell surface and intracellular proteins, and analysis revealed a unique protein cluster profile for each tumor, with a range of 11 to 29 clusters. The researchers then identified a total of 13 metaclusters that seemed to represent the most common phenotypes. Furthermore, each cluster was associated with disease subtypes and behavior.
As for the clinical implications of these research findings, the authors found the protein profile for metacluster 1 contained high CD45 expression and low BCL2 expression, and it was associated with better treatment response and overall survival. Patient profiles without cluster 1 had reduced overall survival (2.2 years vs. 9.4 years, P = .017), indicating that tumors with this profile may be more responsive to treatment in a clinical setting. The authors validated their results by using data from the APEX phase III clinical trial, finding similar survival responses from tumors with high CD45 and low BCL2 expression. Metacluster 13, on the other hand, contained increased expression of proliferative markers and was more frequently found in samples of relapsed or refractory multiple myeloma tumors. The authors suggested that patients with tumor profiles may benefit from antiproliferative therapy.
Disclosure: For full disclosures of the study authors, visit www.nature.com.