Unraveling a Multiple Myeloma Mystery by Studying Bone Lesions

Two reports were published over the past week that merit note to unravel a mystery of multiple myeloma. Both reports provided summaries and details of research done at Roswell Park Comprehensive Cancer Center that has provided new insights into Multiple Myeloma.

The first report was published in the journal Nature Communications and makes for an interesting but difficult read.

The second report comes directly from Roswell Park and it translates the journal article in Nature in language that we, patients, can readily understand.

The second report starts with a historical note:

“In 1873, Russian doctor J. von Rusitzky coined the term "multiple myeloma" after finding eight different types of bone marrow tumors in a single patient.” [emphasis added]

In “Myeloma 101” we learn, “Multiple myeloma is a cancer of the plasma cell, a type of white blood cell present in the bone marrow that makes antibodies to fight infection. In patients with myeloma, plasma cells proliferate too rapidly, crowding out healthy cells and causing painful areas of bone damage called osteolytic lesions.”

The question as to why these cancerous cells cause painful bone disease in some, but not in other, areas of the body has remained unanswered over the past century and a half. The researchers at Roswell Park have now provided a molecular and biological explanation that  “different myeloma clones can be present in a single patient and linking these distinct genetic changes in myeloma cells to the development of myeloma bone disease.”

We (patients) will, most likely, remember the process of our myeloma diagnosis all too well: bloodwork, a bone marrow biopsy aspirated from our hipbone and a PET/CT scan to confirm the presence of bone lesions.

The researchers at Roswell Park went one step further - pulling bone/bone marrow samples directly from the areas where bone lesions were present, guided by the information from the scans. Several hundred thousand cells, obtained from the sites of bone lesions were then analyzed using “a laboratory technique that can identify treatment-resistant clones and subpopulations responsible for metastatic spread.”

Analysis of these samples revealed the following:

• “Myeloma cells from different locations in the same patient are genetically different, especially in patients with relapsed disease.”
• “… subclusters of malignant myeloma cells that overexpressed genes associated with proliferation and oxidative phosphorylation [Phosphorylation is the most common mechanism of regulating protein function and transmitting signals throughout the cell.], two hallmarks of cancer associated with poorer outcomes.”
• “… analyses of individual malignant plasma cells after the patients completed myeloma therapy, [showed] genetic changes in the malignant plasma cells that remained after therapy—changes likely associated with treatment resistance—[this may] also identify new strategies to eradicate treatment resistance in the future.”
• “In addition to genes that have previously been associated with myeloma, the investigators identified a new gene, LAMP5, that is overexpressed in bone lesions and most likely contributes to disease progression.” This may possibly become a target for future therapies, yet to be developed.
• Qualifying myeloma from bone marrow samples pulled only from the hipbone does not give a complete picture of the disease. The authors noted that it is also important to sample specific bone lesions, based on information from PET/CT imaging, “… to identify treatment-resistant clones, … especially when designing targeted, personalized therapies.” [emphasis added]

Jens Hillengass, MD, the lead investigator is quoted as saying:

 "If we want to cure myeloma, then we need to include whole-body imaging in routine follow-up, because without modern imaging techniques like PET and CT, doctors might underestimate the true extent of the disease." [emphasis added]

On numerous occasions in the past the Myeloma Crowd by HealthTree, has been clear that multiple myeloma is a heterogeneous disease, typically interpreted as “we (patients)  are all different from each other”. But the heterogeneity goes beyond that. The Nature paper is a reminder to ALL of us that our disease is also heterogeneous within ourselves . As patients we need to understand that, most likely,  we have different myelomas in different spots of our system and that these myelomas will change in time driven by genetic reaction to our treatment program.

Let me finish with this quote from one of the papers referenced earlier, “The team's findings enhance the current understanding of multiple myeloma, with implications for the treatment and monitoring of patients with both newly diagnosed and relapsed disease. They highlight the possibility to personalize treatment based on the distinct genetic makeup of myelomas [plural] in each patient, both at initial diagnosis and over time.”