Program: Oral and Poster Abstracts
Session: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II
BM samples were collected with the support of the internal medicine and clinical hematology departments of Nice CHU to study the expression of Bcl-B protein in the plasma cell population. BM extracts were separated into 2 parts: 1) 3 millions cells were used to measure Bcl-B expression level by flow cytometry. For this purpose, we performed successively an intracellular (Bcl-B) and an extracellular (CD138+ plasma cells) staining. For each patient, results were expressed as the percentage of plasma cells (CD138+) expressing intracellular Bcl-B marker. 2) The remaining cells were subjected to CD138 positive magnetic sorting to isolate plasma cells. The quantification of Bcl-B protein in the plasma cells was performed in this case by semi-quantitative Western blot experiment.
Between March 2011 and July 2015, 68 BM extracts were analyzed. Among these patients, the median age was 70 years with a sex ratio 1:1. We studied the expression of Bcl-B in 3 healthy individuals, 21 MGUS (Monoclonal Gammopathy of Undetermined Significance) patients, 15 MM patients at diagnosis and 1 patient suffering plasma cell leukemia. In addition we analyzed 7 samples from MM patients treated with first-line therapies and 21 samples from relapsed MM patients. Using flow cytometry, we determined that the average expression of the Bcl-B protein was 3.66% within the plasma cell population of healthy individuals, 4.56% in MGUS patients, 53.56% in newly diagnosed MM patients and 99% in untreated plasma cell leukemia. In addition, the average expression of Bcl-B protein in the plasma cell population was 9.14% in MM patients treated with first-line therapies and 50.33% in relapsed MM patients. Western Blot experiments performed with CD138+ sorted plasma cells revealed an overexpression of Bcl-B protein in newly diagnosis and relapsed MM patients and in patients suffering plasma cell leukemia. MGUS and MM patients treated with first-line therapies revealed a low expression of Bcl-B.
In conclusion, thanks to the BM patients samples collected with the support of the internal medicine and clinical hematology departments of the Nice CHU, we showed overexpression of the anti-apoptotic Bcl-B protein in MM patients at diagnosis or after relapse compared to patients with MGUS. Importantly, the Bcl-B protein was undetectable in MM patients that respond to first-line therapies. Altogether, these results, combined with those obtained from our transgenic mice Eμ-Bcl-B model, suggest that Bcl-B protein could be a new diagnostic marker for MM and a pertinent tool to predict the quality of response treatment.
Disclosures: No relevant conflicts of interest to declare.
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