Multidisciplinary team of experts unraveling the mystery of multiple myeloma

2022-08-06 0 By

In 1873, Russian physician J. Von Rusitzky coined the term “multiple myeloma” after finding eight different types of myeloma in one patient.Nearly 150 years later, the use of advanced cell sequencing technology, and the most advanced imaging technology, researchers at the roswell park comprehensive cancer center offers molecules and biological explanations for this finding, found that there may be different in patients with a single myeloma cloning, and myeloma cells of different genetic changes associated with the development of myeloma bone disease.Multiple myeloma is a cancer of plasma cells, a type of white blood cell found in the bone marrow that produces antibodies to fight infection.In myeloma patients, plasma cells proliferate too quickly, crowding out healthy cells and creating painful areas of bone damage known as osteolytic lesions.But why do cancer cells in multiple myeloma patients cause debilitating bone disease in some parts of the body, while others are unaffected?This has been an unknown quantity for years.The research team was composed of multidisciplinary experts, unprecedented in a prospective clinical trial of this kind, including Jens Hillengass, M.D., Chief of the Myeloma Division, and Philip McCarthy, m.D., Director emeritus of Transplantation and Cell Therapy at Roswell Park Comprehensive Cancer Center.By combining single-cell RNA sequencing with image-guided biopsy of myeloma bone disease lesions, we found significant spatial heterogeneity in patients with relapsed/refractory, newly diagnosed multiple myeloma.The study was published on February 10 in Nature Communications:Deciphering spatial genomic heterogeneity at a single cell resolution in multiple myeloma”The study links the accumulation of malignant, pathogenic plasma cells to the development of myeloma bone disease, providing answers to long-standing questions in multiple myeloma research that may change the way the disease is diagnosed and treated. “multidisciplinary part in research methods have revealed multiple myeloma heterogeneity of important information about space and time.We found that myeloma cells differ on individual cells in individual patients, both in different bone marrow regions and at different times.”Hillengass, PhD, and corresponding author of the study.To further confirm the diagnosis of multiple myeloma, cancer specialists usually obtain a bone marrow biopsy from the iliac crest (hip bone) without the guidance of imaging techniques.In this prospective clinical trials, roswell park comprehensive cancer center experts using the most advanced whole-body imaging technology (PET – CT) not only for 10 cases of asymptomatic patients with multiple myeloma iliac crest biopsies, and to identify and myeloma bone lesions biopsy (7 newly diagnosed cases, 3 cases relapse/refractory cases).Next, integrated Cancer Center researchers from the departments of medicine, immunology, diagnostic radiology, biostatistics, bioinformatics, flow cytometry and image cytometry, clinical cytogenetics, and Pathology and laboratory medicine teamed up with scientists at the Dana-Farber Cancer Institute to use single-cell RNA sequencing,Hundreds of thousands of myeloma cells obtained during image-guided biopsy were analyzed.The analysis showed that myeloma cells in different parts of the same patient were genetically different, especially in patients with recurrent disease.The researchers identified a subpopulation of malignant myeloma cells that overexpress genes associated with proliferation and oxidative phosphorylation, two cancer markers that are associated with poorer prognosis.Dissolved from the bone lesions and get live plasma cells in bone marrow imaging guided biopsy when the team completed in patients with multiple myeloma treatment after repeated analysis of single malignant plasma cells, they found that after treatment of residual malignant plasma cells appeared genetic changes may be associated with resistance to treatment, this suggests that the single-celled sequencing not only can be used for identification and characterization of residual lesions,It can also be used to determine what strategies should be used to make treatment work for patients in the future.In addition to the previously identified gene associated with myeloma, the researchers also identified a new gene LAMP5, which is overexpressed in bone lesions and is likely associated with disease progression.Since the collection of myeloma cells from the iliac crest alone does not provide a complete picture of the disease, obtaining additional information from the imaging to identify therapeutic resistant clones may become standard practice, especially when designing targeted, personalized therapies, the authors note.”Our work highlights the importance of whole-body imaging in the diagnosis and treatment of myeloma because of strong evidence of the presence of different myeloma clones in individual patients.If we want to cure myeloma, then we need to add full-body imaging to our routine follow-up.””Says lead author Maximillian Merz, MD, who led the study while a faculty member at Roswell Park Comprehensive Cancer Center.The team’s findings enhance the current understanding of multiple myeloma and have implications for the treatment and monitoring of both newly diagnosed and relapsed patients.They emphasize that it will be possible to personalize the treatment according to the different genetic makeup of each patient’s myeloma, both at the time of initial diagnosis and later in treatment.Reference data: