Molecular Pathogenesis and a Consequent Classification of Multiple Myeloma

2005 ◽  
Vol 23 (26) ◽  
pp. 6333-6338 ◽  
Author(s):  
P. Leif Bergsagel ◽  
W. Michael Kuehl
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cyclin D1 ◽  
Strong Dependence ◽  
Expression Patterns ◽  
Global Gene Expression ◽  
Immunoglobulin M ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells

There appear to be two pathways involved in the pathogenesis of premalignant non-immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Nearly half of tumors are nonhyperdiploid, and mostly have one of five recurrent IgH translocations: 16% 11q13 (CCN D1), 3% 6p21 (CCN D3), 5% 16q23 (MAF), 2% 20q12 (MAFB), and 15% 4p16 (FGFR3 and MMSET). The remaining hyperdiploid tumors have multiple trisomies involving chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, and infrequently one of these five translocations. Although cyclin D1 is not expressed by healthy lymphoid cells, it is bi-allelically dysregulated in a majority of hyperdiploid tumors. Virtually all MM and MGUS tumors have dysregulated and/or increased expression of cyclin D1, D2, or D3, providing an apparent early, unifying event in pathogenesis. The patterns of translocations and cyclin D expression (TC) define a novel classification that includes eight groups: 11q; 6p; MAF; 4p; D1 (34%); D1+D2 (6%); D2 (17%); and none (2%). The hyperdiploid D1 group is virtually absent in extramedullary MM and MM cell lines, suggesting a particularly strong dependence on interaction with the bone marrow microenvironment. Despite shared progression events (RAS mutations, MYC dysregulation, p53 mutations, and additional disruption of the retinoblastoma pathway), the phenotypes of MGUS and MM tumors in the eight TC groups is determined mainly by early oncogenic events. Similar to acute lymphocytic leukemia, MM seems to include several diseases (groups) that have differences in early or initiating events, global gene expression patterns, bone marrow dependence, clinical features, prognosis, and response to therapy.

scholarly journals Increased expression of cyclin-D1 on trephine bone marrow biopsies independently predicts for shorter overall survival in patients with multiple myeloma treated with novel agents

2012 ◽  
Vol 87 (7) ◽  
pp. 734-736 ◽  
Author(s):  
Anna Tasidou ◽  
Maria Roussou ◽  
Evangelos Terpos ◽  
Efstathios Kastritis ◽  
Maria Gkotzamanidou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Novel Agents ◽  
Bone Marrow Biopsies

scholarly journals A Case of Lymphocytic Leukemia in a Bearded Dragon (Pogona vitticeps) and a Review of Literature

2019 ◽  
Vol 69 (3) ◽  
pp. 360-368
Author(s):  
Alessandra Gavazza ◽  
Livio Galosi ◽  
Veronica Croce ◽  
Amerio Croce ◽  
Carla Genovese ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Immunocytochemical Staining ◽  
Review Of Literature ◽  
Blood Smears ◽  
Bearded Dragon ◽  
Pogona Vitticeps ◽  
Lymphoid Infiltration ◽  
Lymphoblastic Cells

Abstract The present paper reports the case of a 3 years old, female Bearded Dragon (Pogona vitticeps) presenting lethargy, anorexia, weight loss, and anemia and marked leukocytosis at CBC. The majority of leukocytes were lymphocytic/lymphoblastic cells (97%). Immunocytochemical staining of blood smears marked for CD3 (neg) and CD79a (pos) suggested immunophenotype B. The patient died after one month from diagnosis. Histology evidenced lymphoid infiltration in the heart, spleen, liver, kidneys and gut. In addition, in the bone marrow a massive infiltration of lymphoid cells confirmed the diagnosis of leukemia. Immunohistochemistry confirmed the CD79a positivity of a large part of infiltrating lymphoid cells indicating a B cells immunophenotype of the neoplastic population. The presence of lymphocytosis and multiorgan infiltration supported the diagnosis of lymphocytic leukemia. Finally, a revision of the literature has also been made.

scholarly journals Chronic lymphocytic leukemia (CLL) terminating in multiple myeloma: report of two cases

Blood ◽  
1978 ◽  
Vol 52 (3) ◽  
pp. 532-536 ◽  
Author(s):  
RH Kough ◽  
AZ Makary
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Plasma Cells ◽  
Medical Center ◽  
White Male ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
White Female ◽  
Pathologic Fractures

Abstract Two cases of multiple myeloma (MM) developed late in the course of chronic lymphocytic leukemia (CLL). An 81-yr-old white female developed, after 6 yr of CLL, IgAk MM with sheets of plasma cells abutting sheets of lymphocytes in the bone marrow, multiple pathologic fractures, and 0.26 g/24 free k light chains in the urine. A 74-yr-old white male developed, after 16 yr of CLL, k light chain MM with 20% plasma cells in the bone marrow, multiple panthologic fractures, and 3.7 g/24 hr free k light chains in the urine. In both cases the CLL had responded well to intermittent low-dose chlorambucil therapy, but the MM failed to respond to cyclic melphalanprednisone therapy. A review of 105 cases of CLL seen at the Geisinger Medical Center failed to turn up any other cases of MM developing during the course of CLL. The suggestion that there is an increased prevalence of MM in CLL is an attractive one because both diseases are B cell neoplasms and because of the increased frequency of asymptomatic monoclonal gammopathies in CLL found by others.

scholarly journals The Granulocyte Response to Endotoxin in Patients with Hematologic Disorders

Blood ◽  
1964 ◽  
Vol 23 (5) ◽  
pp. 581-599 ◽  
Author(s):  
JOHN C. MARSH ◽  
SEYMOUR PERRY
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
Bacterial Endotoxin ◽  
Chronic Myelocytic Leukemia ◽  
Hematologic Disorders ◽  
Recent Onset ◽  
Myelocytic Leukemia ◽  
Normal Individuals

Abstract Sixty patients with disorders involving the bone marrow were tested with a purified bacterial endotoxin given intravenously. Their leukocyte and granulocyte responses were evaluated based on criteria established in normal individuals and in patients with leukocytosis. Results in patients with chronic myelocytic leukemia, untreated or in relapse, suggest that adequate granulocyte mobilization may still occur if the disease has been of recent onset or if the count has recently started to rise in spite of therapy. Patients in remission demonstrated adequate granulocyte reserves. Most patients with chronic lymphocytic leukemia in this study responded well with an increase in the number of granulocytes. Patients with multiple myeloma as a group showed inadequate granulocyte mobilization. This study demonstrates that endotoxin testing is useful for the evaluation of bone marrow granulocyte reserves in patients with hematologic disorders.

Volume Localized In Vivo Proton MR Spectroscopy of Multiple Myeloma: Variation of Water-Fat Ratio in Patients Receiving Chemotherapy Correlates with Clinical Response.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4863-4863
Author(s):  
Albert Oriol ◽  
Daniel Valverde ◽  
Jaume Capellades ◽  
Miquel Cabañas ◽  
Carles Arús ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Magnetic Resonance ◽  
Partial Response ◽  
Vertebral Body ◽  
Response To Therapy ◽  
Proton Nuclear Magnetic Resonance ◽  
Lumbar Vertebral Body ◽  
Water Signal ◽  
Water Resonance

Abstract Introduction. Bone marrow magnetic resonance (MR) imaging provides important information i<SPACER size="24">n the evaluation of patients with multiple myeloma (MM) but MR assessment of response to therapy is highly subjective. Proton nuclear magnetic resonance spectroscopy (1H MRS) may be able to measure the ratio of lipid to water resonance signal intensities (LWR) and thus reflect the relative percentages of cellular and fatty bone marrow within a defined three-dimensional volume (voxel). These measurements could be used to quantify the degree of cytoreduction in MM patients. Patients and Methods. Twenty-one consecutive patients (10 male; median age 65 years, range 44–82) with newly diagnosed multiple myeloma underwent a MR exploration of the fifth lumbar vertebral body before the initiation of treatment. Patients completing therapy were reevaluated. Dorso-lumbar imaging studies were carried out in a 1.5T system with a saggital spin-echo T1-weighted sequence (TR 437 ms / TE 15 ms). A 2-cm-thick transverse center section of the L5 lumbar vertebral body was sampled to place the voxel. Spectroscopic data were acquired with a stimulated echo acquisition mode (STEAM) sequence without water suppression with repetition time 5 s and echo time 40 ms. To calculate the area of the water signal, the peak was fit to a single Lorenzian curve centered at 4.75 ppm. The area of the lipid resonances was fit to 3 Lorenzian curves centered at 0.89 (-CH3), 1.34 and 2.2 (-CH2) ppm. The areas obtained were used to calculate the LWR for each voxel. The LWR was defined as the sum of the area of the 3 lipid fitted resonances divided by the area of the fitted water resonance. Results. The spectra showed a water peak and a compounded lipid peak separated by approximately 3.1 ppm. LWRs ranged from 0 to 15 (mean 1.748, SD 3.741). Seven patients were treated with melphalan and prednisone (MP) and 14 received 3 cycles of vincristine, BCNU, cyclophosphamide, melphalan and prednisone alternating with 3 cyles of vincristine, BCNU, doxorrubicin and dexametasone (VBCMP/VBAD). Therapy was interrupted for at least 4 weeks before the MR evaluation. Two patients under MP could not be reevaluated. One patient under VBCMP/VBAD suffered extensive L5 collapse that invalidated a second MR study. Four patients progressed under treatment and only 1 of them could be re-submitted to MR. A patient who achieved a partial response after VBCMP/VBAD refused to undergo a MR re-evaluation. Pre and post treatment MR studies were available in 14 patients (progression 1, no response 3, partial response 3, complete response 7). LWR increased in 11/14 patients (78%) (p=0.034). However, 7/7 (100%) complete responders presented a LWR increase (p=0.018) while only 4/7 (57%) non-responders did. No significant differences were observed among partial responders or patients non-responding or progressing. Conclusions. Changes i LWR as assessed by 1H NMR correlated with response to chemotherapy in patients with multiple myeloma, thus this technique may be used to measure noninvasively the response to treatment in these patients.

Low Dose Thalidomide for the Treatment of Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5146-5146
Author(s):  
Rosane Bittencourt ◽  
Andreia D. Almeida ◽  
Joao R. Friederich ◽  
Flavo Fernande ◽  
Laura Fogliatto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Maintenance Therapy ◽  
Marrow Transplantation ◽  
Low Dose ◽  
Bone Marrow Microenvironment ◽  
Immunoglobulin M ◽  
Remission Induction ◽  
Immunoglobulin Level

Abstract In the last two decades, we have seen a radical change in the therapy and prognosis of Multiple Myeloma (MM). Recent research on the role of the bone marrow microenvironment as integrant part of the biology of MM and the possible therapeutic interference at this level are leading to control and regression of the malignant plasma cell clone with a recognized clinical impact. Thalidomide, an old drug thought to interfere on the bone marrow microenvironment, is active not only for the treatment of refractory patients but also, as was recently shown, for induction and/or remission maintenance therapy. Most of the side effects (somnolence, constipation, fatigue, tremor, bradycardia, edema, and neuropathy) can be managed by reducing the dose and most patients need a dose reduction. The appropriate dose of thalidomide in myeloma is unknown. We treated thirty-five patients with MM with low-dose thalidomide (200mg or less). Twenty four patients were on maintenance therapy (13 after bone marrow transplantation, and 11 after chemotherapy with VCAP/VMCP); 5 patients were treated after relapse, 4 with refractory disease and 2 for remission induction as a first line therapy. Patients were treated at the Hematology and Bone Marrow Transplantation Service of the Hospital de Clínicas de Porto Alegre, RS, Brazil, from march/2001 to December/2003. The response as measured by hemoglobin level, immunoglobulin (M component) or urinary light chain concentration and bone marrow examination was evaluated before, 3, 6, and 12 months after the beginning of thalidomide. Results: All patients are alive and well. Fifty one percent are on 100mg schedule; of the patients on maintenance therapy 90% are on complete remission or on a sustained plateau. A Wilcoxon ranks test for the immunoglobulin level before and after 6 months for the entire group showed p=0.001 (25–75%). Conclusion: Low dose thalidomide is tolerable and effective.

C-met Receptor as a Potential Target for the Treatment of Patients with Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3395-3395
Author(s):  
Marcin Majka ◽  
Artur Jurczyszyn ◽  
Anna Zebzda ◽  
Wojciech Czogala ◽  
Ewa Lesko ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Lines ◽  
Protein Level ◽  
Bone Marrow Cells ◽  
Response To Therapy ◽  
Poor Responders ◽  
Met Receptor ◽  
Potential Target ◽  
Marrow Cells

Abstract Despite progress in the treatment of Multiple Myeloma (MM), it is still an incurable disease with average survival of 3–4 years. Because MM is often resistant to conventional therapies, new treatment strategies are necessary. The presence of elevated HGF (Hepatocytic Grow Factor) expression has been well documented in multiple myeloma. The c-met oncogene has been shown to be present in MM cell lines at the mRNA and protein level. Some data suggested that this axis could be responsible for proliferation and inhibition of apoptosis in MM cells. In this study we have analyzed c-met expression in 15 patients with (MM) before and after treatment. Seven of these pts responded well and eight pts responded poorly to the employed therapy. All 15 pts were c-met positive before therapy. Bone marrow cellularity of patients who responded well was 76% before (range: 10% – 100%) and 46% after treatment (range: 40% – 60%). In this group plasmocyte infiltration of bone marrow consisted of 59% before (range: 10% – 80%) and 9% after chemotherapy (range: 0% – 20%). Five of them had undetectable c-met positive cells among bone marrow cells after treatment. In the group of poor responders cellularity of bone marrow was 40% (range: 20% – 70%) before treatment and 46% (range: 20% – 70%) after therapy. Plasmocytes consisted of 20% (range: 10% – 50%) of bone marrow cells before and 44% (range: 10% – 90%) after treatment. All patients in this group had cells positive for c-met receptor after therapeutic regiment. This results suggested that c-met-HGF axis might be a good target for alternative therapy in MM. We looked for potential therapeutics that interferes with this axis and we found that geldanamycin (GA) has been shown to decrease expression of c-met at the protein level in several different cell types. Using inhibitors that belongs to geldanamycin family (GA, 17AAG and 17DMAG) we treated MM cell lines and primary sample. We found that these molecules strongly inhibited expression of c-met in both MM cell lines and patients sample as assessed by western blot analysis. We also tested the influence of these inhibitors on proliferation of MM cells. We found that 100nM dose of GA and 17DMAG inhibited growth of MM cell lines by 80% and 100nM dose of 17AAG inhibited growth of these cells by 20%. Primary cells were more resistant to treatment but we still obtained 30% inhibition with GA and 17DMAG. 17AAG was ineffective and proliferation decreased by less than 10%. Grow inhibition was probably not only due to c-met-HGF axis blockade because these molecules also inhibit other proteins (AKT, RAF). In our experiments we have shown that the level of c-met expression correlates with response to therapy. Patients who respond well had substantially decreased number of c-met positive plasmocytes after chemotherapy in comparison to poor responders. We have also showed that drugs that block c-met-HGF axis could be used in treatment of MM. These drugs could potentially inhibit cells proliferation, increase apoptosis and disrupt MM cells interaction with bone marrow environment. Based on these data we postulate that the c-met receptor is a potential target for MM therapy especially in patients who do not respond to the first line of treatment.

MicroRNA Changes Occur in Multiple Myeloma Cells in the Context of Bone Marrow Milieu.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1785-1785 ◽  
Author(s):  
Roccaro M. Roccaro ◽  
Antonio Sacco ◽  
Abdel Kareem Azab ◽  
Feda Azab ◽  
Hai Ngo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Expression Patterns ◽  
Mirna Gene ◽  
Marrow Stromal Cells ◽  
Stem Loop ◽  
Mirna Profiling ◽  
Qrt Pcr

Abstract Abstract 1785 Poster Board I-811 Background We and Others have previously demonstrated that primary multiple myeloma (MM) cells are characterized by a specific microRNA (miRNA) signature compared to the related normal plasmacell counterpart; and that miRNAs play a crucial role in regulating MM pathogenesis. Nevertheless, miRNA changes that occur in MM cells in the context of the bone marrow microenvironment have not been previously examined. Therefore, characterization of miRNA profiling of MM cells in conjunction with bone marrow stromal cells (BMSCs) is important to better understand the underlying molecular changes that lead to initiation and progression of this disease. Methods We performed miRNA-expression-profiling of MM cell lines (MM.1S; RPMI8226) that were co-cultured with primary BMSCs obtained from 5 MM patients, using liquid phase Luminex microbead miRNA profiling (Luminex, Austin, TX). The expression patterns of unfiltered data were performed using unsupervised hierarchical clustering of samples, based on centroid linkage and 1-correlation distance metric, using dChip (www.dchip.org). To further define those miRNAs differentially expressed between groups (patients vs normal), the data were filtered on significance of differences using ANOVA test, (P < 0.05). Microbead-miRNA profiling data were validated data by stem-loop qRT-PCR. To identify specific predicted miRNA-targeted mRNAs, TargetScan, PicTar, and miRanda algorithms were used. Results miRNA profiling of MM cells cultured with primary BMSCs (MM+BMSC system) differs from MM cells which were not grown in contact with primary BMSCs (MM cells alone). Specifically, we observed increased expression of miRNA-450, -432*, -299-5p, -409-3p, -29b, -542-5p, -184, -517*, -218, 128b, -142-5p and -211 (P<0.05) in MM cells obtained from the MM+BMSC system, compared to MM cells alone. Stem-loop qRT-PCR was performed on matched samples and showed expression patterns similar to those observed in miRNA analysis. Using algorithms commonly used to predict human miRNA gene targets (miRanda; TargetScan; PicTar), predicted targets of the increased miRNAs included negative regulators of NFkB, PI3K/Akt/mTOR, and MAPK/ERK signaling pathways, such as PTEN, KSR2, TWEAK, and DUSP; as well as tumor suppressors (MCC, TSSC1, TUSC1, FBW7, RHOBTB), pro-apoptotic factors and cyclin-dependent kinases inhibitors. These data demonstrate that bone marrow stromal cells exert a modulatory effect on miRNA profiling in MM cells, which results in promoting MM cell growth and reducing MM cell survival. Disclosures Ghobrial: Millennium : Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.

Increased Expression of Cyclin-D1 on Trephine Bone Marrow Biopsies Independently Predicts for Shorter Overall Survival In Patients with Multiple Myeloma Treated with Novel Agents

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2965-2965
Author(s):  
Evangelos Terpos ◽  
Maria Roussou ◽  
Anna Tasidou ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Cyclin D1 ◽  
Plasma Cells ◽  
Univariate Analysis ◽  
Novel Agents ◽  
Positive Staining ◽  
Newly Diagnosed ◽  
Immunohistochemical Expression

Abstract Abstract 2965 The cyclin-D1 proto-oncogene is an important cell regulator of G1 to S phase progression. The overexpression of cyclin-D1 has been linked to the development and progression of several malignancies. The aim of our study was to evaluate the impact of the immunohistochemical expression of cyclin-D1on the plasma cells of trephine biopsies on survival of newly-diagnosed patients with multiple myeloma (MM) who were treated with novel agents. We evaluated formalin-fixed, paraffin-embedded, bone marrow sections of 130 consecutive patients with newly-diagnosed MM (67M/63F; median age 68 years) before any kind of therapy administration. One hundred and fifteen patients had symptomatic disease that required therapy: 29 (25%) received bortezomib-based regimens and 31 (26%) received thalidomide-based regimens as first line therapy, while all patients received regimens containing bortezomib or an IMiD at some point during the course of their disease. Immunohistochemistry was performed in all trephine biopsies using monoclonal antibodies against cyclin-D1 (Cell Marque Corp., Rocklin, CA, USA), but also against CD56 (Cell Marque Corp., Rocklin, CA, USA), CD27 (Novocastra, Newcastle upon Tyne, UK), CD117 and MUM-1 (DAKO A/S, Glostrup, Denmark), as recommended by the manufacturers. A case was considered positive if there was unequivocal positive staining of at least 20% of the plasma cells for cyclin-D1, CD56 and MUM-1 and a positive staining of at least 10% of the plasma cells for CD117 and CD27. Among patients with symptomatic myeloma (N=115), positive staining for cyclin-D1 was found in 35 (30%) patients, for CD56 in 45 (39%), for CD117 in 94 (81%) and for CD27 in 72 (62%) patients. In patients with asymptomatic myeloma, positive staining for Cyclin-D1 was found only in 1 (7%) patient, for CD56 in 9 (64%), and for CD117 in 6 (43%) (p<0.01 for all comparisons compared to symptomatic patients). There were significant positive correlations between positivity for CD27 and CD56 (p<0.001), between positivity for cyclin-D1 and CD117 (p=0.045) and a negative correlation between positivity for CD117 and CD56 (p=0.001). We also observed significant correlations between CD56 positivity and ISS-1 or ISS-2 (p=0.01) and between CD117 positivity and ISS-3 disease (p=0.002). The median overall survival (OS) for patients with symptomatic MM was 57 months (range 22–120 months). In the univariate analysis, positivity for cyclin-D1 (41 vs. 62 months, p=0.03) and for CD117 (50 vs. 75 months p=0.018) were associated with inferior survival, while positivity for CD56 (47 vs. 62 months, p=0.286), MUM-1 (52.7 vs. 63.8 months, p=0.528) and CD27 (57 vs. 50 months, p=0.445) were not. Other factors associated with inferior OS, in the univariate analysis, included ISS-3 (median OS 37 months, vs. 57 months for ISS-2 and 73 months for ISS-1, p=0.005), Hb <10 g/dl (56 vs. 73 months, p=0.044), corrected serum calcium >11.5 g/dl (29 vs. 62 months, p=0.02), serum LDH above upper normal limit (31 vs. 61 months, p=0.05), serum creatinine >2 mg/dl (26 vs. 64 months, p=0.007), low platelet counts (<100,000/ml) (22 vs. 62 months, p=0.031) and age >65 years (45 months vs. not reached for younger patients, p=0.002). In the multivariate analysis, positivity for cyclin-D1 (HR: 2.6; p=0.001), ISS stage (HR: 1.8; p=0.001) and age >65 (HR 2.7, p=0.003) were independently associated with inferior survival. Immunohistochemistry for cyclin-D1 identified subgroups of patients in ISS-2 and in ISS-3 who had extremely poor outcome. Patients with cyclin-D1 positivity had a median survival of 22 months in ISS-2 (vs. 64 months for the rest of ISS-2 patients, p=0.01) and of 13 months in ISS-3 (vs. 47 months for the rest of ISS-3, p=0.012). Our findings underline that the immunohistochemical expression of cyclin-D1 in the bone marrow trephine biopsies has independent prognostic value in MM patients, even in the era of novel agents. This marker can easily be assessed in patients who undergo a trephine biopsy as part of their initial evaluation and offers significant prognostic information. Furthermore, novel agents targeting cyclin-D1 may be of therapeutic value in MM. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document