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)

Two adult cases of the Fanconi syndrome are described, in each of which there was abnormal urinary excretion of immunoglobulin kappa-chain. The significance of this finding is discussed in relation to the recognized association between multiple myeloma and the Fanconi syndrome.
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PMID:Adult Fanconi syndrome with monoclonal abnormality of immunoglobulin light chain. 601 86

The myeloma variant NS-1n has lost the functional immunoglobulin kappa gene which is present in its parent, myeloma MOPC-21. The variant retains a nonfunctional rearranged gene, M.21N, which undergoes RNA transcription and processing to yield a mature size kmRNA. This kRNA, however, is not translated into kappa polypeptide chains. The nonfunctional gene was cloned into Charon 4A to determine the basis for its inactivity. Nucleotide sequence analysis of a DNA fragment overlapping the V-J recombination site in the M.21N gene indicated that a misalignment had taken place during somatic recombination. This misalignment results in a deletion of four nucleotides at the 3' end of the V gene and, thus, a translational reading frame shift. In other respects the M.21n V gene, which corresponds to a different VK subgroup than the functional gene of MOPC-21, appears normal.
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PMID:Misalignment of V and J gene segments resulting in a nonfunctional immunoglobulin gene. 616 85

The principle of mRNA purification by hybridization to an immobilized DNA fragment was applied to the isolation of mRNA coding for immunoglobulin kappa-chains of mouse myeloma MOPC 21 and mouse hybridoma PTF-02. The DNA fragment comprising the 3'-untranslated region and a part of the constant region of the kappa-chain gene was covalently attached to diazobenzyloxymethyl-cellulose and used as an affinity adsorbent. A homogeneous 14S mRNA species was obtained by hybridization of total mRNA to the affinity adsorbent at 52 degrees C and by elution at 60 degrees C. Addition of the purified mRNA to a fractionated cell-free translation system resulted in a significant increase in the radioactivity immunoprecipitated by pig anti-mouse immunoglobulin antibodies. A single radioactive polypeptide of apparent Mr of 25,000, corresponding obviously to the kappa-chain, was identified as the only translation product.
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PMID:Purification of mRNA for immunoglobulin kappa-chains from myeloma and hybridoma cells using hybridization to immobilized complementary DNA. 642 1

Multiple myeloma (MM) is a disease of terminally differentiated B lineage cells and thus alterations in circulating B cells may be anticipated. We studied peripheral blood B cells by flow cytometry in 45 untreated MM patients and compared the results to 25 age-matched controls. The total lymphocyte count and the absolute number and percentage of CD20+ cells were significantly decreased in MM patients. Analysis of the relative amounts of CD20+ cells expressing surface immunoglobulin kappa or lambda light chain isotype did not show either clonal B cell excess or light chain isotype suppression. The percentages of CD10+ and CD20+10+ cells were low both in MM patients and in controls. We consider that the CD20+ cells analysed in this study mainly consisted of normal polyclonal B cells. However, the percentage of the CD20+ cells in the peripheral blood of MM patients was a prognostic factor for survival, both as a continuous and as a dichotomized variable.
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PMID:Peripheral blood B lymphocytes in multiple myeloma. 751 7

Multiple myeloma (MM) remains an incurable disease regardless of recent advances in the field. Therefore, a substantial unmet need exists to treat patients with relapsed/refractory myeloma. The use of novel agents such as daratumumab, elotuzumab, carfilzomib, or pomalidomide, among others, usually cannot completely eradicate myeloma cells. Although these new drugs have had a significant impact on the prognosis of MM patients, the vast majority ultimately become refractory or can no longer be treated due to toxicity of prior treatment, and thus succumb to the disease. Cellular therapies represent a novel approach with a unique mechanism of action against myeloma with the potential to defeat drug resistance and achieve long-term remissions. Genetic modification of cells to express a novel receptor with tumor antigen specificity is currently being explored in myeloma. Chimeric antigen receptor gene-modified T-cells (CAR T-cells) have shown to be the most promising approach so far. CAR T-cells have shown to induce durable complete remissions in other advanced hematologic malignancies like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). With this background, significant efforts are underway to develop CAR-based therapies for MM. Currently, several antigen targets, including CD138, CD19, immunoglobulin kappa (Ig-Kappa) and B-cell maturation antigen (BCMA), are being used in clinical trials to treat myeloma patients. Some of these trials have shown promising results, especially in terms of response rates. However, the absence of a plateau is observed in most studies which correlates with the absence of durable remissions. Therefore, several potential limitations such as lack of effectiveness, off-tumor toxicities, and antigen loss or interference with soluble proteins could hamper the efficacy of CAR T-cells in myeloma. In this review, we will focus on clinical outcomes reported with CAR T-cells in myeloma, as well as on CAR T-cell limitations and how to overcome them with next generation of CAR T-cells.
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PMID:Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma. 3258 4

Minimal residual disease (MRD) assessment is of high clinical relevance in patients with mantle cell lymphoma (MCL). In mature B-cell malignancies, the presence of somatic hypermutations (SHM) in Variable-Diversity-Joining Heavy chain (VDJH) rearrangements leads to frequent mismatches between primers, probes, and the target, thus impairing tumor cells quantification. Alternative targets, such as immunoglobulin kappa-deleting-element (IGK-Kde) rearrangements, might be suitable for MRD detection. We aimed at evaluating the applicability of IGK-Kde rearrangements for MRD quantification in MCL patients by real-time quantitative polymerase chain reaction (RQ-PCR)/digital-droplet-PCR (ddPCR). IGK screening was performed on bone marrow samples from two cohorts: the first from Turin (22 patients enrolled in the FIL-MCL0208 trial, NCT02354313) and the second from Rome (15 patients). IGK-Kde rearrangements were found in 76% (28/37) of cases, representing the sole molecular marker in 73% (8/11) of IGH-BCL1/IGH negative cases. MRD RQ-PCR monitoring was possible in 57% (16/28) of cases, showing a 100% concordance with the conventional targets. However, the frequent background amplification affected the sensitivity of the assay, that was lower in MCL compared to acute lymphoblastic leukemia and in line with multiple myeloma published results. ddPCR had a good concordance with RQ-PCR and it might help to identify false positive/negative results. From a clinical perspective, we suggest that IGK-Kde can be a candidate target for MRD monitoring and deserves a validation of its predictive value in prospective MCL series.
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PMID:Immunoglobulin kappa deleting element rearrangements are candidate targets for minimal residual disease evaluation in mantle cell lymphoma. 3281 26


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