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

The surface expression of CD117 antigen (c-kit) on plasma cells from 158 multiple myeloma (MM), 12 plasma cell leukemia (PCL), 7 MGUS, 7 IgM lymphoplasmacytic lymphoma patients and 10 healthy subjects has been analyzed by flow cytometry using triple staining with the monoclonal antibodies CD138, CD117 and CD38. The antigen expression intensity was calculated as relative fluorescence intensity (RFI) and for direct quantitative analysis the QuantiBRITE test (Becton Dickinson) was applied. Antibody bounding capacity (ABC) was calculated using QuantiCALC software. CD117 antigen was present in 49/158 MM, 5/12 PCL and 5/7 MGUS patients. The RFI values ranged from 0.2 to 20.2 in particular MM patients (mean: 11.0+/-5.3; median 11.5) while the number of CD117 binding sites (ABC) on MM plasma cells ranged from 637 to 6217 (mean: 3029+/-1568; median 2946) (r=0.8328). In responsive to chemotherapy c-kit positive MM patients the percentage of CD117+ plasma cells in the bone marrow decreased significantly while in c-kit negative MM patients the percentage of CD117+ cells in bone marrow did not change and remained in the normal limits. When comparing the clinical and biological disease characteristics (monoclonal protein isotype, albumin, beta2-microglobulin, lactate dehydrogenase, stage of disease, response to chemotherapy, survival time) of c-kit positive and c-kit negative cases, no significant differences were found. In CD117 positive PCL cases expression of CD117 was detected in bone marrow plasma cells as well as in peripheral blood plasma cells. Normal plasma cells and those in IgM lymphoplasmacytic lymphoma did not show reactivity for the CD117 antigen. We conclude that it may be rationale to consider usefulness of therapy with tyrosine kinase inhibitors in the management of c-kit positive plasma cell proliferations. In one third of MM and PCL patients c-kit antigen could be considered as a "tumor associated marker" and together with CD38 and CD138 it may be of value for the identification of the malignant clone in minimal residual disease as it was first suggested by Spanish authors.
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PMID:C-kit receptor (CD117) expression on plasma cells in monoclonal gammopathies. 1551 18

The evaluation of minimal residual disease (MRD) is critical in the evaluation of treatments aimed at maximal cytoreduction in multiple myeloma (MM). Qualitative evaluation of MRD now has a 10-yr-long history, but it remains a relatively sophisticated procedure. More recently, real-time quantitative approaches have also been developed. These approaches allow a very effective monitoring of disease but introduce additional complexity and costs to the procedure. This chapter describes how we currently perform real-time polymerase chain reaction (PCR) in MM. Compared to the first description of the assay in June 2000, significant improvements have been made. Although real-time PCR is the main focus of the chapter, most of the information suitable for a proper setup of a qualitative approach is also provided.
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PMID:Real-time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in myeloma. 1596

Analysis of Ig genes in B-cell malignancies has become an essential method in molecular diagnosis, and polymerase chain reaction (PCR) amplification of Ig heavy chain gene (IgH) rearrangements is now widely used for detection of clonality and minimal residual disease (MRD). Although several different sensitive protocols are now available for PCR analysis of IgH genes, they are frequently hampered owing to the high rate of somatic hypermutation present in multiple myeloma (MM). We recently described a new approach using incomplete DJH rearrangements as an alternative target. About 60% of MM samples contain an incomplete DJH rearrangement, 90% of them lacking on somatic mutations. This approach allows resolution of problems derived from primer mismatches, making DJH rearrangement a reliable and sensitive target for detection of clonality and MRD investigation in MM.
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PMID:Incomplete DJH rearrangements. 1596 1

This study evaluates the prognostic value of molecular monitoring of minimal residual disease (MRD) in 20 patients with multiple myeloma (MM) following autologous (peripheral blood stem cell transplantation, PBSCT) and non-myeloablative allogeneic (NMT) transplant. All patients completed their program, with a treatment-related mortality (TRM) of 20% and a 2-year progression-free survival (PFS) of 51%. After PBSCT, only 3 patients (15%) achieved PCR-negativity, versus 12 (60%) after NMT. The eradication of MRD had a favorable impact on 2-year OS. In fact, 76% of patients with no detectable MRD was still alive versus 34% of persistently IgH-positive cases (p=0.03). PCR status did not correlate with chimerism percentage: Seventy-five percent of patients achieved full donor chimerism, which was more frequently observed in cases presenting cGHVD (p=0.01). These data sustain the relevant role of molecular monitoring in MM patients undergoing NMT. MRD monitoring would assist physicians in making additional therapeutic decisions to better control this hematological malignancy.
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PMID:Prognostic role of minimal residual disease in multiple myeloma patients after non-myeloablative allogeneic transplantation. 1597 48

TCR gamma/delta profiles were analyzed in 13 multiple myeloma patients after allogeneic non-myeloablative transplantation. Results show that both aGVHD and minimal residual disease (MRD) eradication did significantly affect TCR gamma/delta profile. During follow-up, six patients developed an aGVHD episode; in five of them, this event fitted with a modification of the TCR profile. Eleven patients achieved PCR-negativity during follow-up. In the 90% of them, the appearance of a new predominant TCR peak was concomitant to the disappearance of the IgH clone. These results suggest that different T gamma/delta populations would sustain GVM and GVH effects after non-myeloablative allogeneic transplant.
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PMID:Different gamma/delta T clones sustain GVM and GVH effects in multiple myeloma patients after non-myeloablative transplantation. 1624 28

Contamination of autologous graft by tumor, in addition to incomplete tumor eradication, can partly explain why relapse remains the commonest cause of treatment failure after autologous stem cell transplantation (ASCT) in patients with malignant hematologic disorders. Monitoring of minimal residual disease (MRD) is now recognized as an important diagnostic tool for assessment either of the response to treatments aimed at maximal cytoreduction and the individual risk of relapse. In order to improve cure rates, many strategies to achieve in vivo or in vitro reduction, if not eradication, of residual disease have been proposed. We discuss the significance of MRD and the role of purging in the ASCT setting, focusing on acute myeloid leukemia, chronic myeloid leukemia, multiple myeloma and follicular lymphoma.
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PMID:The significance of minimal residual disease in stem cell grafts and the role of purging: is it better to purge in vivo or in vitro? 1626 60

Cumulative clinical experience suggests that immunotherapy may be an effective tool for eradicating tumor cells resistant to maximum tolerated doses of chemotherapy and radiation. Immunotherapy is much more effective when applied at the stage of minimal residual disease, especially against slowly growing tumors because development of graft-versus-leukemia, lymphoma, myeloma, or in a broader sense graft-versus-tumor effects renders immunotherapy more time consuming. Hence, eradication of rapidly growing bulky tumors may be difficult or impossible to achieve. Considering the fact that optimal immunotherapy may be accomplished in patients treated at the stage of minimal (MRD) disease, in patients with hematological malignancies and chemosensitive solid tumors a stage of MRD may be best achieved following administration of myeloablative high-dose chemotherapy or chemoradiotherapy supported by autologous stem cell transplantation (autoSCT). Taken together, immunotherapy following autoSCT may provide an ideal combination for improving the cure rate of otherwise incurable cancers, especially if tumor cells may respond to cytokine-mediated immunotherapy or cell-mediated cytokine-activated immunotherapy. Following lymphocyte depletion in the course of autoSCT, adoptive transfer of alloreactive or tumor-reactive lymphocytes may be much more effective due to the preponderance of anticancer effector cells on the one hand, and elimination or depletion of the patient's regulatory cells that may downregulate anticancer effector mechanisms.
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PMID:Allogeneic cell-mediated immunotherapy at the stage of minimal residual disease following high-dose chemotherapy supported by autologous stem cell transplantation. 1626 61

Although Wilm's Tuomor gene (WT1) was first identified as a tumor suppressor gene for Wilm's tumor, WT1 overexpression has been detected in different malignant cell types including leukemia. Increased expression of WT1 in acute leukemia is potentially used as a marker of minimal residual disease. However, the significance of the gene for multiple myeloma is still not clear. To determine the clinical relevance of WT1 expression in multiple myeloma, we examined the association of clinical parameters and WT1 expression in bone marrow for 17 newly diagnosed multiple myeloma patients. WT1 was assessed by real-time quantitative polymerase chain reaction (RQ-PCR) and calculated standardized WT1 expression level per 100 plasma cells in the bone marrow specimen as "corrected WT1". The expression of standardized WT1 and corrected WT1 in myeloma was 59 to 1,600 copies/microg RNA and 0.05 to 406.3 copies/microg RNA/100 plasma cells, respectively, lower than in leukemia. WT1 transcripts increased when clinical factors worsen, including the stage, amount of M protein, Hb, platelet count, blood urea nitrogen (BUN), creatinine, serum alkaline phosphatase (ALP), calcium, beta2-microglobulin, thymidine kinase activity (TK), and C-reactive protein (CRP). In conclusion, the expression level of WT1 could be an additional marker to the standard parameters considered in risk assessment for multiple myeloma.
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PMID:WT1 expression level and clinical factors in multiple myeloma. 1647 22

Monitoring multiple myeloma patients for relapse requires sensitive methods to measure minimal residual disease and to establish a more precise prognosis. The present study aimed to standardize a real-time quantitative polymerase chain reaction (PCR) test for the IgH gene with a JH consensus self-quenched fluorescence reverse primer and a VDJH or DJH allele-specific sense primer (self-quenched PCR). This method was compared with allele-specific real-time quantitative PCR test for the IgH gene using a TaqMan probe and a JH consensus primer (TaqMan PCR). We studied nine multiple myeloma patients from the Spanish group treated with the MM2000 therapeutic protocol. Self-quenched PCR demonstrated sensitivity of >or=10(-4) or 16 genomes in most cases, efficiency was 1.71 to 2.14, and intra-assay and interassay reproducibilities were 1.18 and 0.75%, respectively. Sensitivity, efficiency, and residual disease detection were similar with both PCR methods. TaqMan PCR failed in one case because of a mutation in the JH primer binding site, and self-quenched PCR worked well in this case. In conclusion, self-quenched PCR is a sensitive and reproducible method for quantifying residual disease in multiple myeloma patients; it yields similar results to TaqMan PCR and may be more effective than the latter when somatic mutations are present in the JH intronic primer binding site.
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PMID:Application of self-quenched JH consensus primers for real-time quantitative PCR of IGH gene to minimal residual disease evaluation in multiple myeloma. 1682 10

The present definition of complete remission (CR) in myeloma is not adequate. The definition is mainly based on measuring the secreted product of myeloma cells (M protein), which has a high interpatient and intrapatient variability, rather than on direct measurement of the remaining tumor load. Polymerase chain reaction (PCR) techniques are very sensitive to measure minimal residual disease, but in myeloma such a technique is very costly and labor intensive because a specific probe needs to be generated for each patient. There is preliminary evidence, based on a limited number of patients analyzed, that specific PCRs are better predictors of outcome in myeloma than the presently used definition of hematologic CR. Our limited experience indicates that with intensive therapy, including tandem transplants, a high percentage of patients in hematologic CR also achieve a molecular CR. The time to disease progression of such patients appears to be significantly longer compared to that of patients not achieving a molecular CR.
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PMID:What is the significance of molecular remission in multiple myeloma? 1734 96


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