Matrix Metalloproteinase and Tissue Inhibitor of Metalloproteinases Is Associated with Multiple Myeloma Progression, Prognosis and Extramedullary Plasmacytoma

Backgrounds and Aims: Matrix metalloproteinase (MMP) is endopeptidase enzyme degrading extracellular matrix, and tissue inhibitor of metalloproteinases (TIMP) is negative regulator of MMP. MMP is well known to be involved in metastatic mechanism of cancer cell and oncogenesis. However expression and role of MMP and TIMP has not been well established in multiple myeloma (MM). Therefore we examined whether expression of MMP and TIMP was involved in progression and prognosis of MM and extramedullary plasmacytoma (EMP) formation.Materials and Methods: Purified bone marrow plasma cells by using anti-CD138 antibody and magnetic beads obtained from 151 MM, 64 MGUS, 18 control and 5 EMP were subjected to the study after informed consent. The study was approved by IRB following Declaration of Helsinki. Whole transcriptome by next generation sequencer (NGS) using Illumina Next Seq 500 was performed in part of the samples to select genes to be studied, then expression level of MMP and TIMP determined by RQ-PCR Delta Ct value normalized with ACTB was used for analysis. MM cell lines KMS11, KMS12PE, KMS12BM, KMM1, RPMI8226, MM1S were used for the in vitro study.Results: We selected TIMP-1, 2and MMP14, 24 based on transcriptome analysis data comparing MM and EMP. The expression level of TIMP1 and MMP24 was significantly higher in MM (median delta Ct: 0.033 for TIMP1, 0.00025 for MMP24) than in MGUS (median delta Ct: 0.013 for TIMP1, 0.00006 for MMP24) (p=0.005, p=0.001), however TIMP2, MMP...
Source: Blood - Category: Hematology Authors: Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster II Source Type: research

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Authors: Kumar SK, Callander NS, Hillengass J, Liedtke M, Baljevic M, Campagnaro E, Castillo JJ, Chandler JC, Cornell RF, Costello C, Efebera Y, Faiman M, Garfall A, Godby K, Holmberg L, Htut M, Huff CA, Kang Y, Landgren O, Malek E, Martin T, Omel J, Raje N, Sborov D, Singhal S, Stockerl-Goldstein K, Tan C, Weber D, Johnson-Chilla A, Keller J, Kumar R Abstract The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, workup, treatment, follow-up, and supportive care for patients with monoclonal gammopathy of renal significance, solitary plasmacytoma, smoldering myeloma, and multiple myeloma. T...
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
ConclusionsThis is the largest study examining outcomes of patients with plasmacytoma using a large database analysis, revealing unique aspects of P-EM versus P-bone and underutilization of radiation treatment.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
ConclusionsThis is the largest study examining outcomes of patients with plasmacytoma using a large database analysis, revealing unique aspects of P-EM vs. P-bone and underutilization of radiation treatment.
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
This is the largest study examining outcomes of patients with plasmacytoma, using the National Cancer Data Base. Clinical and patient-related factors impacting overall survival were studied for both bone and extramedullary plasmacytoma. Patients with bone plasmacytoma who were treated at academic facilities had improved overall survival. Surprisingly, we found radiation treatment was underutilized in patients with solitary lesions, especially in those older than 75 years and with increasing distance from treatment facility.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Original Study Source Type: research
A query regarding the definition and the classification of solitary plasmacytoma is apparently still pending. The clinical course, the response to treatment and the propensity to progress to plasma cell myeloma, are all a function of the classification which must be established on a firm basis. Solitary plasmacytoma should be recognized in the continuum of the plasma cell neoplasms. Moreover, whether the solitary plasmacytoma of bone and the extramedullary type of the tumor represent two distinct disease entities, exhibiting separate biological characteristics, has not been finally established. To appraise the similarities...
Source: Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Abstract Immunoglobulin heavy chain (IgH) translocations are common and early oncogenic events in B cell and plasma cell malignancies including B cell non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). IgH translocations bring oncogenes into close proximity with potent enhancer elements within the IgH locus, leading to oncogene up-regulation. As IgH enhancer activity is tightly controlled by B cell lineage-specific signaling and transcriptional networks, we hypothesized that IgH enhancers are potentially druggable targets/elements. To test this, we developed a molecular imaging-based high-throughput screening...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Tags: Cancer Biol Ther Source Type: research
We examined factors associated with upfront RT in a multivariable logistic model. We then examined the association between upfront RT and overall survival (OS) in a proportional hazard model adjusting for age, sex, race, income, insurance status, comorbidity index, year of diagnosis, type of treating hospital, and time from diagnosis to start of therapy.ResultsOf the 88,995 patients with myeloma, 15,223 (18%) received upfront RT, at median 15 days from diagnosis. Median radiation dose was 3000 cGy delivered over median 10 fractions, with the most common targets being spine/skull (59%), hips/pelvis (12%), and other bones (1...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster II Source Type: research
Conclusion: PTLD is a heterogeneous group of immunodeficiency-associated lymphoproliferative disorders. The overall survival in non-destructive, polymorphic, and monomorphic PTLD were similar. Monomorphic T/NK cell types had inferior outcomes.Figure.DisclosuresMaurer: Morphosys: Research Funding; Nanostring: Research Funding; Celgene: Research Funding. Ansell: Celldex: Research Funding; Merck &Co: Research Funding; Takeda: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Res...
Source: Blood - Category: Hematology Authors: Tags: 627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Retrospective/Observational Studies: Population Based Outcomes in Aggressive Lymphoma Source Type: research
Tumor-lysis syndrome (TLS) describes a group of metabolic disturbances caused by the massive and abrupt release of cellular components into the blood after the rapid lysis of malignant cells. TLS is a potentially life-threatening complication in rapidly proliferating, bulky tumor, or highly chemo-radiosensitive cancers. In contrast, TLS is the rare complication among patients with multiple myeloma (MM). TLS seems to occur more frequently in MM patients receiving bortezomib (BOR) and carfilzomib (CFZ) than in those receiving other cytotoxic agents. We retrospectively investigated the frequency, risk factors, and clinical ou...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation Source Type: research
Conclusion: These data suggest that ISA plus VRd followed by ISA plus Rd is well tolerated with a high ORR of 93%. All responders had VGPR or CR except 1 pt with PR. Quality of CR may have been underestimated due to ISA interference which could be resolved with an interference assay.Funding: SanofiDisclosuresOcio: Janssen: Consultancy, Honoraria; AbbVie: Consultancy; BMS: Consultancy; Pharmamar: Consultancy; Takeda: Consultancy, Honoraria; Seattle Genetics: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Sanofi: Research Funding; Mundipharma: Research Funding; Celgene: Consul...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Antibodies and Targeted Therapies Source Type: research
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