Cell surface marker heterogeneity in human myeloma cell lines for modeling of disease and therapy

Abstract

Multiple myeloma (MM) is a hematological malignancy originating from plasma cells. Genetically, MM is categorized into two subtypes: hyperdiploid and non-hyperdiploid tumors, with distinct chromosomal characteristics. Human myeloma cell lines (HMCLs) are instrumental in understanding MM and identifying therapeutic targets. However, their utility depends on their resemblance to patient-derived cells. We analyzed protein expression of cell surface markers, including myeloma drug targets and immunotherapy-relevant markers, in nine HMCLs using flow cytometry. RNAseq analysis was performed to correlate protein expression with transcriptomic data. While five cell surface markers (CD47, CD49d, CD138, CD269 (BCMA), and GPRC5D) were highly expressed and three (CD19, CD20, and CD117) were low or negative across cell lines, heterogenous expression was observed for the 16 remaining markers. A comparative study with patient-derived transcriptomic data indicated that four of our six in-house HMCLs closely resembled patient disease. Furthermore, our hyperdiploid HMCLs correlated better with hyperdiploid than non-hyperdiploid patient samples. Here, we also describe three previously uncharacterized HMCLs; IH-1, URVIN and FOLE. Our findings underscore the importance of evaluating surface protein expression in HMCLs when modeling MM. The observed variations in expression levels emphasize the need for a strategic selection of cell lines based on the study’s objectives.