Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have raised a murine IgM monoclonal antibody (MA6) against immunoprecipitate obtained by reacting the serum of an NPC patient with extract of the Burkitt lymphoma cell line, Raji. It reacts against an antigen (BLCa) which is broadly represented on human B lymphoid tissues and cell lines but is different from the functional B-cell markers such as surface immunoglobulins, Ia products, Fc and complement receptors. BLCa was found to occur on lymphoid cell lines representing all stages of B-cell differentiation. These included the pre-B and null-cell lines, Nalm 6 and Reh, the EBV-transformed lymphoid cell lines and the myeloma cell line. MA6 was reactive against all the Burkitt lymphoma cell lines, whether or not these harbored the EBV genomes, with the exception of P3HR-I. The antibody was found to be selectively reactive against a proportion of peripheral blood B lymphocytes and to stain the B-cell-rich primary follicles and mantle zones of secondary follicles in the lymph node. However, MA6 was not reactive against cell lines of T-lymphocyte, myeloid, monocyte fibroblast or epithelial origin. It did, nevertheless selectively stain tumor cells from a variety of carcinoma tissues originating from different anatomical sites, including the nasopharynx.
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PMID:A shared antigenic determinant between human B lymphocytes and carcinomas (BLCa). 241 75

NK cells and alphabeta- and gammadelta-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in gammadelta-CTL and EBV-specific alphabeta-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-gamma was lowest in the patient group, whereas IL-12, IL-15 and TNF-alpha were produced in higher levels in patients than in the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was also higher than that of the donors and survivors. Furthermore, the patients at later stages of NPC had lower gammadelta-CTL activity but higher NK cytotoxicity towards NPC targets, with higher production of IL-12, IL-15 and TNF-alpha but lower production of IFN-gamma than in patients at earlier stages. This might be part of a triggered compensatory re-activation of the innate immunity, believed to be mediated through various cytokines and chemokines when adaptive T cell immunity is breached. Together, these data suggest complementary roles of innate and adaptive immune response in tumor immunity where NK cells, gammadelta- and alphabeta-CTL compensate for the deficits of one another at different stages of tumor invasion.
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PMID:Complementary activation of peripheral natural killer cell immunity in nasopharyngeal carcinoma. 1680 22

Monoclonal gammopathy of undetermined significance (MGUS) can progress to multiple myeloma (MM). Although these diseases share many of the same genetic features, it is still unclear whether global gene-expression profiling might identify prior genomic signatures that distinguish them. Through significance analysis of microarrays, 52 genes involved in important pathways related to cancer were differentially expressed in the plasma cells of healthy subjects (normal plasma-cell [NPC]; n=22) and patients with stringently defined MGUS/smoldering MM (n=24) and symptomatic MM (n=351) (P<.001). Unsupervised hierarchical clustering of 351 patients with MM, 44 with MGUS (24+20), and 16 with MM from MGUS created 2 major cluster branches, one containing 82% of the MGUS patients and the other containing 28% of the MM patients, termed MGUS-like MM (MGUS-L MM). Using the same clustering approach on an independent cohort of 214 patients with MM, 27% were found to be MGUS-L. This molecular signature, despite its association with a lower incidence of complete remission (P=.006), was associated with low-risk clinical and molecular features and superior survival (P<.01). The MGUS-L signature was also seen in plasma cells from 15 of 20 patients surviving more than 10 years after autotransplantation. These data provide insight into the molecular mechanisms of plasma-cell dyscrasias.
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PMID:Gene-expression signature of benign monoclonal gammopathy evident in multiple myeloma is linked to good prognosis. 1702 74

We retrospectively reviewed the flow cytometry (FCM) data from bone marrow aspirates of multiple myeloma (MM) patients before and after autologous stem cell transplantation (ASCT). Light scatter properties and CD38 expression were used to identify plasma cells, and CD19/CD45/CD56 further distinguished normal from abnormal plasma cells (NPC and APC, respectively), the latter defined as plasma cells with aberrant CD56, decreased or absent CD19 and/or CD45 expression. Forty-seven patients were screened. After ASCT, 66% (31/47) patients achieved complete remission (CR)/very good partial remission (VGPR), as compared to only 40% (19/47) prior to ASCT (P = 0.01). In 39 patients with data before and after ASCT, all 39 (100%) had a detectable APC population prior to ASCT. Twenty-six out of 39 patients (67%) also had detectable NPC. Following ASCT, the number of patients with detectable NPC increased to 35/39 (89%), while 3/39 (8%) had no detectable NPC and 1/39 (3%) had neither NPC nor APC. The proportion of APC decreased significantly after transplant from a median of 79% to 52% post-transplant (P < 0.001). The APC/total events ratio decreased significantly (P < 0.0001) after transplant. Prior to transplant, patients with less than 1.8% APC had significantly longer progression free survival (PFS) than patients with greater than 1.8% (P = 0.017, by log rank test), while the difference in overall survival did not achieve statistical significance (P = 0.081). Patients who achieved CR/VGPR after transplant had significantly longer PFS in comparison to all others (26 months vs. 11 months, P = 0.004). In conclusion, the detection of a significant population of APC by FCM prior to ASCT significantly correlates with poorer PFS in MM patients.
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PMID:Flow cytometric minimal residual disease monitoring in patients with multiple myeloma undergoing autologous stem cell transplantation: a retrospective study. 1823 1