scholarly journals Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them

2021 ◽  
Vol 22 (3) ◽  
pp. 1103
Author(s):  
Marco Cippitelli ◽  
Helena Stabile ◽  
Andrea Kosta ◽  
Sara Petillo ◽  
Angela Gismondi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Immunomodulatory Activity ◽  
Cancer Cell Growth ◽  
Cytotoxic Effects ◽  
Growth And Survival ◽  
Therapeutic Implications ◽  
Development And Differentiation ◽  
Innate Lymphocytes

The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.

The Role of Stromal Cells in Multiple Myeloma: Actors or Spectators?.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2506-2506
Author(s):  
A. Corso ◽  
E. Ferretti ◽  
A. Gallì ◽  
A. M. Tenore ◽  
C. Pascutto ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Growth Factors ◽  
Stromal Cells ◽  
Linear Models ◽  
Plasma Cells ◽  
Growth And Survival ◽  
Better Than

Abstract Multiple myeloma (MM) is a B cell neoplasia characterized by an accumulation of clonal plasma cells (PCs) in the bone marrow (BM). The growth and survival of MM plasma cells is regulated by their network with the microenvironment, mainly with the stromal cells. However, although bone marrow stromal cells have been shown to take part in the pathogenesis of the disease, it is still unknown whether these cells play an active or passive role. Namely, whether normal stromal cells simply supply the demand of MM plasma cells, or, during the course of the disease, they acquire abnormal characteristics becoming pathological. To address this question, we designed an in vitro co-culture model in which PCs isolated by immuno-magnetic separation from MGUS and MM patients are crossed with BM stromal cells (BMSCs) derived from MGUS and MM patients. As a result, four type of co-cultures were obtained: MM-BMSCs/MM-PCs, MM-BMSCs/MGUS-PCs, MGUS-BMSCs/MM-PCs, MGUS-BMSCs/MGUS-PCs. After two days of co-culture in a serum free medium, we evaluated the survival of MM-PCs or MGUS-PCs for each combination. We also quantified by ELISA assays in the supernatants of the same cultures, the level of several growth factors (IL-6, IL-8, VEGF, MIP-1a, MIP-1b, RANTES, MCP-1, TGF-b, SDF-1) to evaluate the possible influence of these cytokines on plasma cells. Multivariate general linear models were applied to compare survival in the different combinations of BMSCs and PCs, also accounting for the various growth factors. MM-BMSCs showed to support the survival of both MM-PCs and MGUS-PCs significantly better than MGUS-BMSCs (p=0.0007). However, in the combination MGUS-PCs/MGUS-BMSCs plasma cells survived statistically better than in that MM-PCs/MGUS-BMSCs (p=0.00003). As regards the cytokines, IL-6, IL-8, VEGF, MIP-1a, MIP-1b, and RANTES did not show to be significantly associated with plasma cell survival in all settings. TGF-B and SDF-1 levels were significantly associated with better survival of both MM-PCs and MGUS-PCs when cultured with MM-BMSCs compared to MGUS-BMSCs (p=0.0001 and p=0.038, respectively), while MCP-1 was significantly associated with reduced survival of MM-PCs and MGUS-PCs in the same setting (p=0.006). In conclusion, these data favours the concept that the behaviour of stromal cells may change during the transition from the condition of MGUS to the overt state of myeloma, evolving from a simple role of a spectator to that of an actor. It also appears that overt MM plasma cells have the highest need for cytokine supply and therefore are more dependent on BMSCs activity.

scholarly journals The Role of Translation Control in Tumorigenesis and Its Therapeutic Implications

2020 ◽  
Vol 4 (1) ◽  
pp. 437-457
Author(s):  
Yichen Xu ◽  
Davide Ruggero
Keyword(s):  
Cancer Cells ◽  
Cancer Progression ◽  
Mrna Translation ◽  
Translation Control ◽  
Cancer Cell Growth ◽  
Growth And Survival ◽  
Therapeutic Implications ◽  
Key Driver ◽  
Oncogenic Stress

As a convergent mechanism downstream of most oncogenic signals, control of mRNA translation has emerged as a key driver in establishing and tuning gene expression at specific steps in cancer development. Translation control is the most energetically expensive molecular process in the cell that needs to be modulated upon adaption to limited cellular resources, such as cellular stress. It thereby serves as the Achilles’ heel for cancer cells, particularly in response to changes in the microenvironment as well as to nutrient and metabolic shifts characteristic of cancer cell growth and metastasis. In this review, we discuss emerging discoveries that reveal how cancer cells modulate the translation machinery to adapt to oncogenic stress, the mechanisms that guide mRNA translation specificity in cancer, and how this selective mode of gene regulation provides advantages for cancer progression. We also provide an overview of promising preclinical and clinical efforts aimed at targeting the unique vulnerabilities of cancer cells that rely on the remodeling of mRNA translation for their infinite growth and survival.

scholarly journals IL-32 is a metabolic regulator promoting survival and proliferation of malignant plasma cells

2021 ◽  
Author(s):  
Kristin Roseth Aass ◽  
Robin Mjelle ◽  
Martin H. Kastnes ◽  
Synne S. Tryggestad ◽  
Luca M. van den Brink ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Oxidative Phosphorylation ◽  
Plasma Cells ◽  
Inflammatory Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Gene Signature ◽  
Growth And Survival ◽  
Novel Concept

AbstractIL-32 is a non-classical cytokine expressed in cancers, inflammatory diseases and infections. IL-32 can have both extracellular and intracellular functions, and its receptor is not identified. We here demonstrate that endogenously expressed, intracellular IL-32 binds to components of the mitochondrial respiratory chain and promotes oxidative phosphorylation. Knocking out IL-32 in malignant plasma cells significantly reduced survival and proliferation in vitro and in vivo. High throughput transcriptomic and MS-metabolomic profiling of IL-32 KO cells revealed that loss of IL-32 leads to profound perturbations in metabolic pathways, with accumulation of lipids, pyruvate precursors and citrate, indicative of reduced mitochondrial function. IL-32 is expressed in a subgroup of multiple myeloma patients with an inferior prognosis. Primary myeloma cells expressing IL-32 were characterized by a plasma cell gene signature associated with immune activation, proliferation and oxidative phosphorylation. We propose a novel concept for regulation of metabolism by an intracellular cytokine and identify IL-32 as an endogenous growth and survival factor for malignant plasma cells. IL-32 is a potential prognostic biomarker and a treatment target in multiple myeloma.

scholarly journals Biologic sequelae of IκB kinase (IKK) inhibition in multiple myeloma: therapeutic implications

Blood ◽  
2009 ◽  
Vol 113 (21) ◽  
pp. 5228-5236 ◽  
Author(s):  
Teru Hideshima ◽  
Dharminder Chauhan ◽  
Tanyel Kiziltepe ◽  
Hiroshi Ikeda ◽  
Yutaka Okawa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Nuclear Factor Κb ◽  
Down Regulation ◽  
Growth And Survival ◽  
Therapeutic Implications ◽  
Iκb Kinase ◽  
Canonical Pathways ◽  
Promising Treatment

Abstract Nuclear factor-κB (NF-κB) has an important role in multiple myeloma (MM) cell pathogenesis in the context of the bone marrow (BM) microenvironment. In NF-κB signaling cascades, IκB kinase α (IKKα) and IKKβ are key molecules that predominantly mediate noncanonical and canonical pathways, respectively. In this study, we examined the biologic sequelae of the inhibition of IKKα versus IKKβ in MM cell lines. All MM cell lines have constitutive canonical NF-κB activity, and a subset of MM cell lines shows noncanonical NF-κB activity. Adhesion to BM stromal cells further activates both canonical and noncanonical NF-κB activity. IKKβ inhibitor MLN120B blocks canonical pathway and growth of MM cell lines but does not inhibit the noncanonical NF-κB pathway. Although IKKα knockdown induces significant growth inhibition in the cell lines with both canonical and noncanonical pathways, it does not inhibit NF-κB activation. Importantly, IKKα down-regulation decreases expression of β-catenin and aurora-A, which are known to mediate MM cell growth and survival. Finally, IKKβ inhibitor enhances the growth inhibition triggered by IKKα down-regulation in MM cells with both canonical and noncanonical NF-κB activity. Combination therapy targeting these kinases therefore represents a promising treatment strategy in MM.

SUCCESSFUL MANAGEMENT OF SPHENOID RELAPSE OF MULTIPLE MYELOMA WITH RADIATION THERAPY: A CASE REPORT

2021 ◽  
pp. 1-2
Author(s):  
A. Bazine ◽  
M. Torreis ◽  
M. Elmarjany ◽  
M. Benlemlih ◽  
A. Maghous ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Radiation Therapy ◽  
Case Report ◽  
Skull Base ◽  
Plasma Cells ◽  
Complete Disappearance ◽  
Successful Management ◽  
Shed Light

Multiple myeloma (MM) is typically characterized by neoplastic proliferation of plasma cells in the bone marrow and can result in extensive skeletal destruction. Involvement of skull base is extremely rare, especially sphenoid bone. We report in this work the case of a 62-year-old woman, who presented with a sphenoid relapse of multiple myeloma treated with radiation therapy, with signicant clinical improvement and almost complete disappearance of the sphenoid metastasis. We shed light, through this case, on the rarity of sphenoid metastases in multiple myeloma and on the role of radiotherapy in the management of this type of location.

scholarly journals Role of microRNAs in Diagnosis, Prognosis and Management of Multiple Myeloma

2020 ◽  
Vol 21 (20) ◽  
pp. 7539
Author(s):  
Amro M. Soliman ◽  
Teoh Seong Lin ◽  
Pasuk Mahakkanukrauh ◽  
Srijit Das
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Tumor Growth ◽  
Malignant Transformation ◽  
Bone Disease ◽  
Clinical Management ◽  
Potential Role ◽  
Plasma Cells ◽  
The Usa

Multiple myeloma (MM) is a cancerous bone disease characterized by malignant transformation of plasma cells in the bone marrow. MM is considered to be the second most common blood malignancy, with 20,000 new cases reported every year in the USA. Extensive research is currently enduring to validate diagnostic and therapeutic means to manage MM. microRNAs (miRNAs) were shown to be dysregulated in MM cases and to have a potential role in either progression or suppression of MM. Therefore, researchers investigated miRNAs levels in MM plasma cells and created tools to test their impact on tumor growth. In the present review, we discuss the most recently discovered miRNAs and their regulation in MM. Furthermore, we emphasized utilizing miRNAs as potential targets in the diagnosis, prognosis and treatment of MM, which can be useful for future clinical management.

Update on Risk Stratification Model of Smoldering Multiple Myeloma: A Systematic Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5512-5512
Author(s):  
Saad Ullah Malik ◽  
Ahmad Abu-Hashyeh ◽  
Muhammad Sardar ◽  
Mohammad M Alhousani ◽  
Emilia Cindy Leigh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Cell Maturation ◽  
B Cell Maturation ◽  
Smoldering Multiple Myeloma ◽  
Pet Ct ◽  
M Proteins ◽  
Pet Ct Scan ◽  
Bence Jones Proteins

Background: Smoldering multiple myeloma (SMM) was stratified into risk classes based on several models including Mayo clinic and Spanish myeloma working group models. After the revision of diagnostic criteria for multiple myeloma (MM) in 2014, the ultra-high risk SMM patients (>80% clonal plasma cells at two years) were re-classified as active MM patients. Thus, predictors of progression in patients currently diagnosed as SMM are unknown and reassessment of existing models is required. We aim to identify the risk factors associated with progression in SMM patients classified according to updated guidelines. Methods We performed a literature search following PRISMA guidelines and used following bibliographic databases: MEDLINE (Ovid and PubMed), EMBASE, The Cochrane Library and Cochrane Central Register of Controlled Trials (CENTRAL), as well as annual meetings abstracts from inception till 1st,August 2019. We used MeSH and Emtree terms as well as performed open search for "smoldering multiple myeloma", "smoldering myeloma", and "asymptomatic multiple myeloma". Two independent reviewers screened the literature. We used snowballing technique to screen abstracts and reference within articles to include titles. Cochrane collaboration tool was used to asses risk of bias among included studies Results Our search retrieved 419 titles. After going through the titles and abstracts 38 articles were selected for full text review. Final review led to inclusion of 11 articles. Levels of serum M proteins, percentage of bone marrow plasma cells (BMPCs), serum free light chain ratio (FLCr) and PET/CT scan findings of whole body were most consistently and reliably indicated the progression of SMM to MM (Table 1). New studies are suggesting that B-cell maturation levels (BCMA), evolving M-proteins (eMP) and evolving hemoglobin levels (eHb) are also an accurate measure of SMM progression and should be incorporated in the risk stratification models. A study by Gonsalves WI et al. also suggested that levels of circulating clonal plasma cells with a cutoff of 150 was an important prognostic marker in their study. Immunoparesis status and role of Bence Jones proteins in reliably predicting the progression of SMM was debatable because they were significant in univariate analysis but were not significant in multivariate analysis (Table 1). Conclusion Serum M protein levels (2 g/dL), percentage of BMPCs (20%), serum FLCr (20) and PET/CT scan were reliable in predicting the prognosis of smoldering MM. New techniques like B-cell maturation levels(74.4 ng/mL), evolving M-proteins and evolving hemoglobin levels can play a significant role in proposing future risk predictive models of SMM. Role of immunoparesis and Bence Jones proteins is debatable. Table 1 Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

Dysregulated Apurinic/Apyrimidinic Endonucleases (Ape1 and Ape2) Lead to Genetic Instability in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1418-1418
Author(s):  
Masood A. Shammas ◽  
Hemant Koley ◽  
Sima Shah ◽  
Ramesh B. Batchu ◽  
Pierfrancesco Tassone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Homologous Recombination ◽  
Genomic Instability ◽  
Cell Lines ◽  
Plasma Cells ◽  
Dna Recombination ◽  
Endonuclease Activity ◽  
Single Nucleotide ◽  
Genetic Changes

Abstract Multiple myeloma (MM) is associated with significant genomic instability. Homologous recombination (HR), which is elevated in MM, is considered to be responsible for this instability. As endonucleases play an important role in mediating HR, here we have evaluated the role of endonuclease in biology and progression of MM. Gene expression profile using Affymetrix U133 array showed > 2 fold elevation of Ape1 or Ape2 or both in 5 of 6 MM cell lines and 12 of 15 patient samples. Immunocytochemistry confirmed upregulation of Ape1 protein in MM cell lines. A Plasmid degradation assay confirmed significantly elevated endonuclease activity in MM cells compared to normal plasma cells. To identify the pre-dominating endonuclease activity, the degradation assay was carried out in the presence of specific endonuclease inhibitors. Harmane and methoxyamine (MA), specific inhibitors of apurinic/apyrimidinic endonucleases effectively inhibited significant endonuclease activity, while other endonuclease inhibitors ACPD and FK506 had minimal effects, confirming predominant role of apurinic/apyrimidinic endonucleases (APE) in mediating increased endonuclease activity in MM. We investigated the role of elevated APE endonuclease activity on DNA recombination and subsequent genomic re-arrangements. Using a plasmid-based assay we have previously demonstrated significantly elevated homologous recombination (HR) in MM. Inhibition of endonuclease by methoxyamine suppressed HR activity by 85 ± 2% in MM cells. Next, we evaluated whether inhibition of HR by methoxyamine can affect the frequency of acquisition of new genetic changes in MM cells using single nucleotide polymorphism (SNP) arrays (Affymetrix) as indicator of genomic instability. In three independent experiments, methoxyamine reduced the acquisition of new loss of heterozygocity (LOH) loci by an average of 71%. These data suggest that the dysregulated APE endonucleases contribute significantly to the genomic instability, acquisition of new mutations and progression of MM and provides the rationale for targeting endonuclease activity to prevent disease progression including development of drug resistance.

CD27-Mediated Apoptosis Is Dependent on Siva-Induced Caspase Activation in Human Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3398-3398 ◽  
Author(s):  
Yu-Tzu Tai ◽  
Xian-Feng Li ◽  
Rory Coffey ◽  
Iris Breitkreutz ◽  
Laurence Catley ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Death ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Plasma Cells ◽  
Death Domain ◽  
Caspase Activation ◽  
Growth And Survival ◽  
Induced Apoptosis ◽  
Cell Growth And Survival

Abstract CD27, a member of tumor necrosis factor receptor superfamily that lacks a death domain in its cytoplasmic region, and its interaction with its ligand, CD70, is crucial for differentiation into plasma cells. In malignant B cells, aberrant expression and reverse signaling of CD70 might contribute to disease progression. Recent studies showed that CD27 is heterogeneously expressed on multiple myeloma (MM) plasma cells and the expression is reduced with the progression of MM. However, a possible role for the loss of CD27-CD70 interaction in myelomagenesis was never defined. In this study, we identify functional significance of CD27-CD70 interaction in 4 CD27-expressing MM lines and define mechanisms regulating CD27-mediated MM cell death. Using RT-PCR and flow cytometric analysis, we first found that all of MM lines highly express CD70 (n=10) and 4 MM lines 12BM, 12PE, 28BM, 28PE express CD27 on the cell surface. We next evaluated the effect of CD27 ligation, by CD70-transfected NIH3T3 cells (CD70 transfectant), on [3H] thymidine incorporation by CD27-expressing MM lines. CD27 ligation by CD70 transfectants inhibited DNA synthesis in these 4 CD27-expressing MM lines, but not the control transfectants. Conversely, a blocking anti-CD70 mAb blocked CD27-mediated growth inhibition in a dose-dependent manner, indicating induced growth inhibition specific triggered by CD27-CD70 interaction. Using MTT assay, CD27 ligation by CD70 transfectant also inhibited MM cell survival. IL-6 (20 ng/ml) could overcome the inhibitory effect triggered by CD27 ligation on MM cell growth and survival. In addition, CD27 ligation further enhanced Dex-induced MM cell death. Importantly, CD27-mediated MM cell death was also observed in 2 CD27-expressing patient MM cells. Since Siva is a death domain-containing proapoptotic protein identified as an intracellular ligand of CD27, we investigated its role in CD27-mediated apoptosis in MM cells. Overexpression of Siva by transducing adenovirus-expressing Siva (Ad-Siva-GFP) in 12BM MM line is sufficient to induce cell death whereas control adenovirus (Ad-GFP) transduction did not alter 12BM cell growth and survival. CD27 ligation by CD70 transfectants on Siva-overexpressing 12BM cells further enhanced Siva-induced apoptosis, as evidenced by increased subG0 fraction in cell cycle analysis. Thus, the apoptosis triggered by Siva overexpression was related to the CD27-mediated apoptotic pathway. We further determined caspase involvement in the Siva-induced apoptosis in the absence and presence of CD70 transfectants. Caspase 8 and caspase 9 activities were detected 24h following Ad-Siva-GFP transduction in 12BM cells, whereas caspas-3 activity was detected 48h after transduction. Coculture of Ad-Siva-GFP-transduced 12BM cells with CD70 transfectant further enhanced caspase activities. Therefore, overexpression of Siva is sufficient to induce apoptosis and CD27-mediated apoptosis is mediated by Siva-dependent caspase activation in MM. Furthermore, these results suggest that lack of CD27 may lead to evasion of apoptosis in human MM.

Microrna Expression Profile Identifies Distinct Clinically Relevant Sub-Groups in Multiple Myeloma: Novel Prognostic Markers and Potential Targets for Therapy

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 96-96 ◽  
Author(s):  
Sophia Adamia ◽  
Herve AvetLoiseau ◽  
Samirkumar B Amin ◽  
Yu-Tzu Tai ◽  
Steven P. Treon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Differentiation ◽  
Clinical Outcome ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Plasma Cells ◽  
Normal Plasma ◽  
Group A ◽  
Group B

Abstract MicroRNA, an abundant class of small endogenous RNAs, regulate target genes through inducing translational inhibition and cleavage of targeted transcripts. To date, microRNAs have been implicated in normal biological processes, including development, cell differentiation, apoptosis and proliferation as well as in malignant transformation. However, their role in multiple myeloma (MM) remains unknown. Here we investigated role of microRNAs in myelomagenesis, and their influence on prognosis and clinical outcome. We evaluated profiles of 384 microRNAs in bone marrow derived CD138+ plasma cells (PC) from 79 uniformly treated MM patients, 11 MM cell lines and 9 healthy donors using qRT-PCR based microRNA array. The relative expression was calculated using comparative Ct method, and data was normalized using endogenous controls and analyzed using SDS, RQ manager, R and dChip softwares. MicroRNA expression profiles detected in MM patients were correlated with clinical outcome measures. We observed significant modulate expression of 61 microRNAs in myeloma cells compared to normal plasma cells. When more stringent criteria were used, we identified 24 differentially expressed microRNAs in patient samples. Further, unsupervised hierarchical clustering of filtered microRNAs, based on their DCt values, identified two major groups within the MM population (groups A and group B). Samples of Group A clusters with MM cell lines, indicating more proliferative nature of MM patient cells. Within B group, a second degree node group B2, clusters with normal plasma cells indicating more indolent course, while patients in an additional node B1 represented an assorted pattern. The unsupervised clustering of all MM samples showed consistent changes in miR-30b, -30c, -30d, -142-5p, -24, -191, -181d, -374, -146b, -140, -145, -125a, -151, -223, -155, let7b, indicative of a role of these microRNA in myelomagenesis; while supervised analysis of samples within groups A and B identified modulated expression of different sets of miRNAs. In group A miR-585 and let-7f were upregulated 8–12 fold, while miRs -125a, -126, -155, -223, -146a, -374 -19a, -20a, -26a, -30a -5p, -30b, and -30d were significantly downregulated; in group B, all differentially expressed microRNAs were downregulated (p<0.001) compared to normal plasma cells. These modulated miRNAs target critical signaling pathways including apoptosis, hematopoietic cell differentiation and proliferation, survival and angiogenesis by upregulating function of HOX9, c-myc, VCAM-1, Bcl-2, E2F1, SHP1, SHP2, VEGF, and DUSp6 molecules. We further analyzed the effect of microRNA on clinical outcome. We have observed significantly superior event free and overall survival of patients in group B2 compared to patients in group A (2 yr estimated EFS 79% versus 54% respectively; p=0.05; and 2 yr estimated OS 94% versus 70% respectively; p =0.017). Taken together this data identifies critical microRNAs as modulators of gene expression and signaling pathways and provides potential novel microRNA and gene targets in MM to both understand biological behavior and for therapeutic application.

Sign in / Sign up

Export Citation Format

Share Document