Analysis of Transcriptome, Mirnome and Genomic Profiles in Association with Clinical Outcome in a Prospective Series of Primary Plasma Cell Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3938-3938 ◽  
Author(s):  
Luca Agnelli ◽  
Pellegrino Musto ◽  
Katia Todoerti ◽  
Marta Lionetti ◽  
Laura Mosca ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Clinical Outcome ◽  
Plasma Cell ◽  
Copy Number ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
Gene Model ◽  
First Line ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 3938 Primary plasma cell leukemia (PPCL) is a rare and very aggressive form of plasma cells dyscrasia, characterized by poorer outcome than multiple myeloma (MM). To provide insights into the biology of PPCL, we investigated 23 newly-diagnosed patients included in an open-label, multicenter, prospective, single arm, two-stage study aiming to explore efficacy and safety of lenalidomide and dexamethasone combination (LD) as first line therapy in previously untreated PPCL (median follow-up: 23 months; range 9–32). The primary endpoint of the study was the response rate, according to the criteria defined by International Myeloma Working Group, after 4-cycle therapy with LD over a 4-month schedule; among secondary endpoints were overall survival (OS) and eligibility to undergo autologous or allogeneic stem cells transplantation (SCT) after LD treatment. Herein, we took advantage of the FISH characterization and the microarray analysis of transcriptome, miRNome and copy number configurations of the PPCLs to investigate whether a correlation could exist between transcriptional features or allelic imbalances and clinical outcome. FISH was used to detect the main IGH translocations. The gene expression profiles of highly purified plasma cells from PPCLs cases were generated on GeneChip® Gene1.0 ST arrays. Expression values were normalized using robust multi-array average (RMA) procedure. MicroRNA profile were generated on Agilent Human miRNA Microarray V2. Expression values were extracted with Agilent Feature Extraction Software v10.1; quantile normalization was applied on raw data using R aroma.light package. GeneChip® Human Mapping 250K NspI arrays was used for genotyping. Copy number was estimated using circular binary segmentation and normalized on FISH data using R DNA.copy and FBN packages, respectively. To assess correlation between expression values and OS, R globaltest package was used to generate the linear regression model in which the distribution of the response variable is modeled as a function of the expression levels of each gene/miRNA. Our analysis indicated that all but three of the PPCLs had one among t(4;14) (13%), t(11;14) (39%) or MAF-associated translocation (35%). However, neither any of them nor any of the numerical alteration involving 1p, 6p, 8p, 13q, 14q, 16q, 17p (loss) and 1q (gain) as assessed by SNP-arrays were correlated with OS. As well, no correlation between response to treatment with LD and the prevalence of these cytogenetic alterations was evidenced. Of the 1145 most variable gene across the PPCL dataset and OS, 27 reached a highly significant correlation (P<.01) with OS. This 27-gene model was able to dissect the PPCL into two groups, one of which containing 6 cases with poorer outcome. In multivariate analysis, this model retained independency from all the cytogenetic alterations, as well as from age, sex, LDH levels, renal function and hematologic parameters. The 27-gene model was not independent of patients being subjected to autologous SCT, indicating that this therapeutic approach points definitively towards a more favorable outcome. Similarly, we assessed the relationship between each of the 114 most variable miRNAs across the dataset and OS. Two miRNAs reached a significant correlation (P<.01) with OS (miR-92a and miR-330–3p), allowing the division of samples into two groups with different outcome. In multivariate analysis, both retained independency from all the cytogenetic alterations [except del(8p) as regards miR-330–3p] and from other parameters, but not from autologous SCT. Finally, three genes (CYB5D2, EDEM3 and YIPF6) and four miRNAs (miR-497, miR-106b, miR-181a* and miR-181b) were identified having expression levels correlated with response to the first-line treatment with LD. Overall, this study represents the first integrated approach on a prospective study investigating genes and miRNAs expression and genotyping configuration in PPCL, indicating specific genes and miRNAs with relevance in the clinical outcome of the disease. Disclosures: No relevant conflicts of interest to declare.

A Pilot Study of Lenalidomide and Dexamethasone as First Line Therapy in Patients with Primary Plasma Cell Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4951-4951
Author(s):  
Pellegrino Musto ◽  
Maria Teresa Petrucci ◽  
Fortunato Morabito ◽  
Francesco Nobile ◽  
Fiorella D'Auria ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Early Response ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Primary Plasma Cell Leukemia

Abstract Abstract 4951 Background Primary Plasma Cell Leukemia (PPCL) is an aggressive, rare variant of multiple myeloma, with clinical, molecular and phenotypic peculiarities, which accounts approximately for 2% to 4% of all myeloma diagnoses. The prognosis of PPCL patients is usually poor, with less than half of patients responding to conventional chemotherapy and a median survival of 7 months. Even by using autologous or allogeneic transplant procedures, survival generally does not exceed three years. Bortezomib has recently provided some promising results in this setting, but, given all the above, new treatments for PPCL are greatly awaited. Lenalidomide is a new immunomodulating agent with great efficacy in multiple myeloma, especially when associated with dexamethasone or other drugs. There are, indeed, some sporadic case reports of PPCL patients treated with lenalidomide as salvage therapy, but no data are currently available on the use of this drug as first line therapy in this disease. Patients and Methods On March, 2009, we started an open label, prospective, multicenter, exploratory, single arm, two-stage study aiming to evaluate safety and antitumor activity of the lenalidomide/low dose dexamethasone combination (Rd), as first line therapy in patients with PPCL. The primary endpoint was early response rate according to International Uniform Criteria. The secondary endpoints were TTP, PFS, OS, percentage of eligible PPCL patients able to collect peripheral blood stem cells and to undergo autologous or allogeneic stem cells transplantation after Rd, serious and severe adverse event rate. According to this study protocol, all eligible, newly diagnosed adult patients with PPCL receive Lenalidomide at a dose of 25 mg daily for 21 days every 28 days. Oral dexamethasone is administered at a dose of 40 mg daily on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, patients who achieve at least PR and not eligible for autologous or allogeneic stem cell transplantation, continue with Rd until clinically appropriate (disease progression, unacceptable toxicity, patient's decision to leave the protocol). In these patients, a maintenance dose of lenalidomide alone equal to 10 mg/die days 1-21 every month is considered after at least 8 full dose Rd cycles. Patients responding after 4 Rd cycles and eligible for transplant procedures, proceed according to single Centre transplant policy. Patients not responding after 4 cycles or progressing under Rd treatment are considered off-study. Appropriate contraception methods and anti-thrombotic prophylaxis are planned. Results Four enrolled patients (1 male, 3 female, mean age 65 years, range 58-69) are currently evaluable for early response. All had unfavourable cytogenetics, including del13, t(4;14), t (14;16), or a complex karyotype. Circulating plasma cells ranged from 4.4 to 9.2 ×10e9/l. One patient had at baseline a moderate degree of renal failure (serum creatinine levels 2 mg/dl). After at least 2 Rd cycles (range 2-4), two PR and two VGPR were achieved (overall response rate 100%), with disappearance or near complete reduction of circulating plasma cells in all cases. The most relevant toxicities were grade 3 neutropenia and pneumonia, occurring in one patient and resolved by appropriate lenalidomide dose reduction, introduction of G-CSF and antibiotic therapy. One patient died in PR, due to causes unrelated to PPCL or treatment. As, according to the Simon, two-stage design adopted, more than two responses occurred within the first ten patients enrolled (stage 1), a total of 22 PPCL subjects will be accrued to complete the stage 2 of the trial. Conclusions These findings, though very preliminary, suggest that the combination of lenalidomide and dexamethasone may be a safe and promising initial therapy for PPCL patients, which can rapidly control the disease and could permit to perform following single patient-adapted therapeutic strategies. An update of this study, including molecular data, a larger number of patients and a longer follow-up, will be presented at the Meeting. Disclosures Musto: Janssen-Cilag: Honoraria; Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide is approved in Italy for advanced multiple myeloma, not for plasma cell leukemia. This is a clinical trial registered at AIFA (Italian regulatory Agency for Drugs), EudraCT No. 2008-003246 28. Petrucci:Janssen-Cilag: Honoraria; Celgene: Honoraria. Morabito:Celgene: Honoraria; Janssen-Cilag: Honoraria. Cavo:Celgene: Honoraria; Janssen-Cilag: Honoraria. Boccadoro:Celgene: Honoraria; Janssen-Cilag: Honoraria. Palumbo:Celgene: Honoraria; Janssen-Cilag: Honoraria.

A RARE CASE PRESENTATION OF PRIMARY PLASMA CELL LEUKEMIA WITH REVIEW OF LITERATURE, A CASE REPORT

2021 ◽  
pp. 21-22
Author(s):  
Gaurav Sharma ◽  
Smita Sharma
Keyword(s):  
Case Report ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Rare Entity ◽  
Cell Leukemia ◽  
Case Presentation ◽  
Blood Examination ◽  
Primary Plasma Cell Leukemia

Introduction: Primary Plasma Cell Leukemia (pPCL) is Plasma cell dyscrasia subtype which is rare and aggressive. It carries very poor prognosis. It has unique clinical and laboratory prole. Its rst clinical presentation is leukemia. Peripheral blood examination shows circulating mature looking yet clonal, plasma cells. On molecular and cytogenetic examinations, many aberrations are seen which are unique and make it a distinct entity different from traditional Multiple Myeloma (MM). Case presentation: 37 yr old Indian female presented with difculty in breathing for last 3 months and was initially evaluated for cardiac function & COVID-19 screening. Peripheral blood examination revealed circulating plasma cells. Bone marrow apirate conrmed the initial diagnosis of pPCL. She received BIODRONATE + Inj. BORTEZOMIB + Inj. CYCLOPHOSPHAMIDE + Tab Dexa and was advised for PETscan and skeletal survey. But due to nancial constraints, family decided to go for complete systemic workup in next phase of chemotherapy cycle. She was discharged with advise to be in close follow up and to complete her treatment cycles. Discussion: pPCL needs to be diagnosed promptly to formulate optimal intensive therapy. This atypical presentation with shortness of breath of rare entity of pPCLin such young age emphasizes the need for quick and thorough initial workup. Conclusion: Because of rarity of this disease, there is paucity of literature from India and especially the impact of the standard therapies in resource poor countries. Our case report highlights these challenges for conclusive management of this rare entity

scholarly journals A life-threatening presentation of primary plasma cell leukemia

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Roma S Fourmanov ◽  
◽  
Annemiek Joosen ◽  
Lidwine Tick ◽  
Heleen S de Lil ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Hemoglobin Concentration ◽  
Plasma Cell Leukemia ◽  
Plasma Cell Dyscrasia ◽  
Bone Lesions ◽  
High Dose ◽  
Cell Leukemia ◽  
Primary Plasma Cell Leukemia

Background: Multiple myeloma is a relatively common type of plasma cell dyscrasia, in which monoclonal plasma cells proliferate. This frequently leads to anemia, renal failure, hypercalcemia and bone lesions. Primary plasma cell leukemia is a much rarer type of plasma cell dyscrasia, with measurable plasma cells in the blood circulation and usually more acute presenting signs. Case: A 57-year-old woman presented to the emergency department with dyspnea. Because of hypoxemia due to a hemoglobin concentration of 3.1 g/dL (1,9 mmol/L), asystole occurred, and cardiopulmonary resuscitation had to be started. The severe anemia turned out to be due to a primary plasma cell leukemia. Palliative treatment was started with combination chemotherapy with VTD (bortezomib, thalidomide and dexamethasone) with a very good partial response, after which she proceeded to an autologous stem cell transplantation with high dose melphalan conditioning. Conclusion: Primary plasma cell leukemia is a plasma cell dyscrasia with both resemblances and differences from the better-known multiple myeloma. It is less common, but presenting signs often are more acute and more severe. Currently there is no curative treatment. Keywords: Plasma cell leukemia; Hematological emergency; Multiple myeloma; VTD.

scholarly journals Efficacy of Venetoclax and Dexamethasone in Refractory IgM Primary Plasma Cell Leukemia with t(11;14) and TP53 Mutation: A Case Report and Literature Review

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Salimah Valliani ◽  
Mir Ali ◽  
Omar Mahmoo ◽  
Sanjay Hinduja ◽  
Calvin K. Chen ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Tp53 Mutation ◽  
Treatment Options ◽  
Proteasome Inhibitors ◽  
Plasma Cell Leukemia ◽  
Cell Leukemia ◽  
First Line ◽  
Uncommon Disease ◽  
Primary Plasma Cell Leukemia ◽  
Good Partial Response

Primary plasma cell leukemia (pPCL) is an uncommon disease. IgM multiple myeloma (MM) is an infrequent subtype that accounts for less than 1 percent of MM cases. IgM pPCL is quite rare with only a few cases published to date. We describe a case of a patient with IgM pPCL who initially presented with hyperviscosity syndrome requiring urgent plasma exchange. His bone marrow biopsy demonstrated t(11;14). He progressed on proteasome inhibitors, immunomodulating agents, and other chemotherapy medications but later achieved very good partial response (VGPR) to venetoclax and dexamethasone. Given the poor prognosis of pPCL, further studies using venetoclax alone or in combination with other novel agents as first-line treatment options are warranted particularly in patients with t(11;14).

Lenalidomide and Low Dose Dexamethasone As First Line Therapy for Newly Diagnosed Patients with Primary Plasma Cell Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 729-729 ◽  
Author(s):  
Pellegrino Musto ◽  
Vittorio Simeon ◽  
Giovanni D'Arena ◽  
Maria Carmen Martorelli ◽  
Maria Teresa Petrucci ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Low Dose ◽  
Response Rate ◽  
Plasma Cell Leukemia ◽  
Hematological Toxicity ◽  
Cell Leukemia ◽  
First Line ◽  
First Line Therapy ◽  
Primary Plasma Cell Leukemia ◽  
Grade 3

Abstract Abstract 729 Introduction: The prognosis of primary plasma cell leukemia (PPCL) remains poor. The “novel agents” have recently shown promising results in PPCL patients in case reports or small retrospective series. Here we describe the first prospective, multicenter, phase II clinical trial of PPCL, where lenalidomide in combination with low dose dexamethasone (Ld) was tested as initial therapy in newly diagnosed patients fulfilling the IMWG diagnostic criteria of PPCL. Patients and methods: Ld regimen consisted of lenalidomide 25 mg/d for 21 days and oral dexamethasone 40 mg on days 1, 8, 15, and 22 for each 28-day cycle. After 4 cycles, responding patients not eligible for stem cell transplantation (SCT) continued until 8 cycles of full-dose Ld, followed by a maintenance dose of single agent lenalidomide equal to 10 mg/d on days 1–21 of each 28-day cycle. Patients responding after 4 cycles and eligible for SCT proceeded according to the treatment centre's transplant policy. Patients not responding after 4 cycles or progressing during this treatment were considered off-study. Appropriate dose reductions (in particular for patients with reduced renal function at baseline), double contraception methods and anti-thrombotic/anti-infective prophylaxis were recommended. The primary end-point was early response rate according to IMWG uniform response criteria. Secondary end-points were PFS, OS, feasibility and efficacy of SCT, safety. Results: According to the Simon optimal two-stage adaptive design, twenty-three patients were enrolled in between March 2009 and May 2011. The male/female ratio was 1.1, and median age was 60 years (range 44–80). The median absolute number and percentage of circulating plasma cells were 4.280/μl (range 1.500–114.660) and 34% (range 21–90) respectively. Fifteen patients (65.2%) had abnormal renal function at presentation. Twenty-one patients (91.3%) were tested by FISH analysis and cytogenetic abnormalities were detected in all of them, del13q being the most frequently found (16 patients). Seventeen patients showed multiple chromosomal lesions. Involvement of chromosome 14 was observed in 18 patients, three of whom showed t(4;14). Chromosome 1q gain and del17p were detected in 10 and 7 patients, respectively. In the intention-to-treat (ITT) population, overall response rate (ORR) after at least one Ld cycle was 73.9% (17/23), with 8 patients (34.7%) achieving partial remission (PR), 5 (21.7%) very good PR (VGPR), 3 (13%) complete response (CR), and 1(4.3%) near CR (nCR) (VGPR or better: 39%). In the efficacy-evaluable (EE) population, 14 out of 15 patients who received the initially planned 4 Ld cycles (65.2% of the ITT population) responded (ORR 93.3%), achieving 5 PR (33.3%), 5 VGPR (33.3%), 1 near-CR (6.6%) and 3 CR (20%) (VGPR or better: 59.9%). The maintenance phase was reached and safely performed in 4 responding patients not eligible for SCT, 3 of whom relapsed after 2, 8 and 22 months, respectively. After Ld induction therapy, 8 patients received single (n. 4) or double (n. 4) autologous SCT (ASCT); another patient underwent a sequence of ASCT followed by non-myeloablative allogeneic SCT (AlloSCT). Six eligible patients did not receive ASCT frontline, due to initial Ld failure or adverse events; three of them underwent single ASCT (n. 2) or tandem ASCT/non-myeloablative AlloSCT (n. 1) after a bortezomib-based salvage therapy, achieving 2 CR and 1 PR. After a median follow-up of 23 months, median OS and PFS in ITT population were not reached and 22 months, respectively. All transplanted patients remained alive, although three of them relapsed and started salvage treatments; OS was 12 months in the 11 patients who did not receive ASCT (p < 0.001). The correspondent figures for PFS were 29 and 16 months, respectively (p < 0.01). Considering ITT population, multivariate analyses showed that SCT was positively correlated to both OS and PFS. There were 17 episodes of grade 3/4 non hematological toxicity, which occurred in 13 patients (5 infections, 3 renal, 3 metabolic, 2 gastro-intestinal, 2 skin, 1 fatigue, 1 thromboembolic), causing early interruption of Ld treatment in 4 patients. Grade 3/4 hematological toxicity (mainly neutropenia) occurred in 11 patients (47.8%). Conclusions: Ld may be a feasible and effective initial therapeutic option for PPCL, particularly in patients who receive ASCT after a short course of induction treatment. Disclosures: Musto: Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide as first line therapy of plasma cell leukemia. Petrucci:Celgene: Honoraria. Cascavilla:Celgene: Honoraria. Di Raimondo:Celgene: Honoraria. Caravita:Celgene: Honoraria. Morabito:Celgene: Honoraria. Offidani:Celgene: Honoraria. Bringhen:Celgene: Honoraria. Boccadoro:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Palumbo:Celgene: Consultancy, Honoraria.

scholarly journals Primary plasma cell leukemia: consensus definition by the International Myeloma Working Group according to peripheral blood plasma cell percentage

2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Carlos Fernández de Larrea ◽  
Robert Kyle ◽  
Laura Rosiñol ◽  
Bruno Paiva ◽  
Monika Engelhardt ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Prognostic Impact ◽  
Cell Leukemia ◽  
Consensus Definition ◽  
Cell Percentage ◽  
Primary Plasma Cell Leukemia

AbstractPrimary plasma cell leukemia (PCL) has a consistently ominous prognosis, even after progress in the last decades. PCL deserves a prompt identification to start the most effective treatment for this ultra-high-risk disease. The aim of this position paper is to revisit the diagnosis of PCL according to the presence of circulating plasma cells in patients otherwise meeting diagnostic criteria of multiple myeloma. We could identify two retrospective series where the question about what number of circulating plasma cells in peripheral blood should be used for defining PCL. The presence of ≥5% circulating plasma cells in patients with MM had a similar adverse prognostic impact as the previously defined PCL. Therefore, PCL should be defined by the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma.

scholarly journals Double-Hit Primary Plasma Cell Leukemia with IGH/MYC and IGH/CCND1 Translocations

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Masato Yasumi ◽  
Takaya Endo ◽  
Hiroshi Sata ◽  
Takahiro Karasuno
Keyword(s):  
Plasma Cell ◽  
Plasma Cells ◽  
Abrupt Onset ◽  
Plasma Cell Leukemia ◽  
The Novel ◽  
Cell Leukemia ◽  
Agent Based ◽  
Primary Plasma Cell Leukemia ◽  
Worse Prognosis

Primary plasma cell leukemia (pPCL) is an aggressive variant of multiple myeloma (MM). Immunoglobulin heavy chain (IgH) translocations are found in a majority of pPCL cases, supporting a central relation to pathogenesis of pPCL. However, two independent IgH translocations are barely detected at the onset of pPCL, and their significance is yet to be elucidated. Here, we report a case of an aggressive pPCL with simultaneous IGH/MYC and IGH/CCND1 translocations. A 73-year-old man was referred to our hospital with back pain and diagnosed as having pPCL with more than 50% circulating plasma cells. Cytogenetic analysis revealed 47, Y, t (X; 8;14) (q24; q24; q32), t (11; 14) (q13; q32), and +18. IGH/MYC and IGH/CCND1 translocations were confirmed by fluorescence in situ hybridization analysis. Bortezomib and dexamethasone treatment achieved rapid elimination of peripheral malignant plasma cells, and the patient maintained a partial response for 18 months. After biological relapse, he received salvage therapy with ixazomib, lenalidomide, and dexamethasone, followed by pomalidomide and dexamethasone, and exhibited stable disease for an additional 14 months. Although IGH/MYC translocation in association with dysregulation of antiapoptotic pathway leads to worse prognosis in lymphomas, the novel agent-based regimen showed good efficacy, suggesting that IGH/MYC plays a different role in the pathogenesis of MM. IGH/CCND1 and IGH/MYC translocations may have contributed to abrupt onset of pPCL in this case.

Implication of the Anti-Apoptotic Protein Bcl-B (BCL2L10) in the Pathogenesis of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2958-2958
Author(s):  
Valentine Richez ◽  
Frederic Luciano ◽  
Amine Hamouda ◽  
Alexandre Puissant ◽  
Guillaume Robert ◽  
...  
Keyword(s):  
Internal Medicine ◽  
Multiple Myeloma ◽  
Cell Population ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Plasma Cell Leukemia ◽  
Healthy Individuals ◽  
Cell Leukemia ◽  
First Line ◽  
Apoptotic Protein

Abstract Multiple myeloma (MM) is a haematological cancer characterized by a malignant plasma cell infiltration restricted to the bone marrow (BM). Bcl-B protein is the last anti-apoptotic member of the Bcl-2 family to be discovered and is mainly expressed in B lymphocytes and human plasma cells. However, its pathophysiologic role is still unknown. Our team has generated a transgenic mouse model (Eμ-Bcl-B) where Bcl-B protein expression is restricted to the B cell compartment; Eμ-Bcl-B mice develop with age a lymphoproliferative syndrome recapitulating all of the human MM characteristics. Following these promising results, we focused our attention on the potential role of Bcl-B protein in the pathogenesis of MM to designate this anti-apoptotic protein as a prognostic marker and eventually as a new therapeutic target. 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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