Abstract
To provide a single molecular assay that could be used to easily stage Multiple Myeloma patients at diagnosis, we investigated the association between the simultaneous expression of 7 Multiple Myeloma-associated Cancer/Testis Antigens and biochemical parameters that are currently used for disease staging. We analysed the mRNA expression of MAGEC1, MAGEA3/A6, BAGE2, PRAME, NYESO1, SSX2 and PAGE by qualitative reverse transcription PCR using RNA extracted from diagnostic bone marrow samples from 39 patients covering the Multiple Myeloma disease continuum and compared this to levels of key biochemical parameters at diagnosis. We found that the Cancer/Testis Antigen panel was expressed in a specific order that was specifically associated with the severity of disease. This allowed the Cancer/Testis Antigens expression profile to successfully place the patient clearly into either stage I or stage III of the disease, with further sub-stratification in the stage III grouping. In addition, we putatively identified MAGEC1 expression as a confirmatory diagnostic marker for symptomatic Multiple Myeloma and clearly associated BAGE2 expression exclusively with stage III disease. We also demonstrated the novel finding of PAGE expression in Multiple Myeloma, with an association with more advanced disease. We suggest that this particular molecular Cancer/Testis Antigen panel can be used at diagnosis as a single test to clearly stage patients.
Highlights
Multiple Myeloma (MM) is a hematological malignancy that is characterized by the accumulation of monoclonal malignant plasma cells in the bone marrow (BM), and elevated serum or urine monoclonal paraproteins
A previous study, using flow cytometry to detect MAGEC1 in PB and BM samples, showed that malignant Cancer/Testis antigens (CTAs) expression in MM is associated with early stem cells (CD34+) and early pro-B to pre-B cells (CD34+/−/CD19+), with only the proliferating compartment of plasma cells expressing the malignant marker [28]
This association was further strengthened by the increase in the number of CTAs expressed by two AMM patients who progressed to MM within 12 months, both showing no CTA expression at initial diagnosis and 3 and 6 genes, respectively at follow up
Summary
Multiple Myeloma (MM) is a hematological malignancy that is characterized by the accumulation of monoclonal malignant plasma cells in the bone marrow (BM), and elevated serum or urine monoclonal paraproteins. The International Staging System (ISS), is based on levels of β2 microglobulin (B2M) and albumin, and the Durie-Salmon Staging (DSS) index that looks at M-protein levels, the presence of bone lesions, haemoglobin (Hb), calcium and serum creatinine levels [8,9]. While both staging systems are fairly successfully in staging disease into 3 large categories, multiple additional tests are required to be able to sub-classify the patients into more specific prognostic subgroups. Is this process expensive, but often not possible due to the range of laboratory expertise that is required and a comprehensive patient prognostic profile is often not achieved
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