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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple myeloma (MM) is the most common plasma cell dyscrasia. Conventional therapy results in a median survival of 3-5 years. Patients with B-cell disorders and coexistent HER-2/neu overexpression in solid tumors have a poorer prognosis than those without an underlying B-cell disorder. This, and the recent success of the tyrosine kinase inhibitor, imatinib mesylate in chronic myelogenous leukemia, led us to evaluate the incidence and role of c-kit (CD117) and HER-2/neu overexpression in MM. We conducted a retrospective study to determine the incidence of HER-2/neu and c-kit overexpression in MM. HER-2/neu overexpression was evaluated using the DAKO Hercep test and c-kit overexpression was assessed using conventional immunohistochemistry (IHC); 69 patients with a diagnosis of MM were identified, of whom, 31 patients (19 males and 12 females) had an adequate pathological specimen available for IHC testing; 4 out of 31 patients (12.9%) showed HER-2/neu overexpression, while 5/31 (16.13%) showed CD117 expression. Two patients (6.45%) showed both HER-2/neu and c-kit overexpression. Although both HER-2/neu and c-kit are not expressed very frequently in patients with MM, there appears to be a subgroup of patients in whom, either one or both these oncogenes is overexpressed. Given our small sample size, it is difficult to comment on the effect of CD117 and/or HER-2/neu overexpression on survival. Future larger studies are needed to define the association in MM and to determine if the presence of one (CD117 or HER-2/neu) has an effect on overexpression of the other oncoprotein. Furthermore, it would be beneficial to identify the molecular nature of the interplay between HER-2/neu and c-kit, if any. Target-directed signal transduction inhibition therapy using tyrosine kinase inhibitors, may be a distinct possibility in a select group of patients with MM.
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PMID:Immunohistochemical identification of HER-2/neu overexpression and CD117 (c-kit) expression in multiple myeloma. 1261 38

Bone marrow aspirates from 306 patients with multiple myeloma were analyzed by flow cytometric immunophenotyping. The plasma cells (PCs) were identified by their characteristic light scatter distribution and reactivity patterns to CD138, CD38, and CD45. Monoclonality was confirmed by immunoglobulin light chain analysis. The immunophenotypic profile of the PCs was determined with a panel of antibodies. Moderate to bright expression of CD56, CD117, CD20, CD45, and CD52 was detected in 71.7%, 17.8%, 9.3%, 8.8%, and 5.2% of cases, respectively. These antigens were expressed by a distinct subpopulation of the PCs in 6.3%, 2.2%, 3.7%, 2.9%, and 2.6% of additional cases. CD19 was negative in more than 99% of cases. The combination of CD38 and CD138 was superior to CD38 alone for identifying CD45+ myeloma and separating CD20+ myeloma from B-cell lymphoma. PC immunophenotyping might be useful for detecting minimal residual disease in cases with aberrant antigen expression and for selection of therapeutic agents that have specific membrane targets.
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PMID:Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. 1508 Feb 99

An association between mastocytosis and monoclonal gammopathy is a relatively rare but well recognized clinical finding. In the majority of cases, however, overt myeloma or lymphoma is not detectable morphologically. Here we describe the case of a 51 year-old male patient first presenting with paresis of the right facial nerve and the serological finding of IgM kappa paraproteinemia. The patient did not have organomegaly, lytic bone lesions, or urticaria pigmentosa-type skin lesions. Histological examination of a trephine biopsy specimen revealed the unusual coexistence of plasma cell myeloma and mastocytosis. Immunohistochemically, plasma cells were found to exhibit a monotypic staining for Ig heavy chain mu and Ig light chain kappa, thus confirming their neoplastic nature. Mast cells showed prominent spindling and formed dense multifocal infiltrates, thus enabling the diagnosis of bone marrow mastocytosis. Immunohistochemically, mast cells expressed tryptase, chymase, and KIT (CD117). In addition, aberrant expression of CD25 on mast cells was detected, confirming the coexistence of a neoplastic mast cell-proliferative disorder. According to the WHO proposal for classification of hematopoietic malignancies, this unique case, showing the association of two very rare haematologic neoplasms, can therefore best be referred to as bone marrow mastocytosis associated with IgM kappa plasma cell myeloma (SM-AHNMD).
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PMID:Bone marrow mastocytosis associated with IgM kappa plasma cell myeloma. 1516 Sep 59

A 70-year-old woman presented with pancytopenia associated with plasma cell infiltration of her bone marrow. The plasma cells were often multinucleated and demonstrated phagocytosis of erythroid and granulocytic cells. Atypical immunophenotypic features included the expression of CD117 and CD13 and the lack of expression of CD56. Although kappa chains were demonstrable in the cytoplasm, no paraprotein was found in the serum or urine. Osteolytic lesions were absent. The pancytopenia of this unusual patient with non-secretory, hemophagocytic myeloma has improved on dexamethasone monotherapy, although her hemophagocytosis persists.
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PMID:Hemophagocytic, non-secretory multiple myeloma. 1529 68

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

Myelomatous plasma cells show a high heterogeneity both in their immunophenotypic characteristics as well as in their cytogenetic features. Thus far, no extensive studies have been carried out to explore whether such antigenic diversity is associated with specific genetic characteristics. We have investigated the relationship between the immunophenotypic profile at plasma cell and both their DNA ploidy status (evaluated by flow cytometry) and specific genetic features (ascertained by fluorescence in situ hybridization) in a large series of 915 patients with newly diagnosed multiple myeloma. The non-hyperdiploid multiple myeloma group (n = 454, 52%) was associated with a significantly higher frequency of positivity for CD28 and CD20 as well as a higher incidence of CD56(-) and CD117(-) cases (P < 0.001). Remarkably, 13q deletion and immunoglobulin heavy chain (IGH) gene rearrangements, which were significantly more common in non-hyperdiploid multiple myeloma, showed a strong association with CD117(-) cases. IGH translocation to 11q13 was associated with reactivity for CD20 (P < 0.001), down-regulation of CD56 (P < 0.001), and lack of expression of CD117 (P = 0.001). By contrast, IGH translocations to other chromosome partners were almost exclusively found among CD20(-) and CD117(-) cases (P < 0.001). These results suggest that genetic categories in multiple myeloma exhibit particular immunophenotypic profiles which in turn are strongly associated with the DNA ploidy status.
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PMID:Genetic abnormalities and patterns of antigenic expression in multiple myeloma. 1589 62

The WHO immunophenotype for plasma cell myeloma is deletion of CD19 and CD20, usual expression of CD38, CD138, and CD56, and occasional expression of CD10. Of the 39 cases of plasma cell dyscrasia in our study, the mean fluorescence intensities (MFI) of CD38, CD138, CD56, and CD19 were quantified in 30 cases. CD19 was absent in 38 of the cases (97.4%), whereas CD138 and CD38 were expressed in all 39 cases (100%). Most cases expressed CD38 and CD138 brightly with MFI values greater than 501, whereas all other marker expression was moderate with MFI greater than 301. Whereas CD38/CD56 dual expression was observed in 25 cases (64.1%), 14 failed to express CD56 (35.9%). CD56 expression was bright in 16 cases (53.3%), moderate in 2 cases (6.7%), and negative in the remaining 12 cases (40%) with MFI values of 200 or less. CD117 expression was positive in 9 of 24 cases (37.5%). In 32 of 39 cases, 27 were negative for CD20 (84.4%) and 28 were negative for CD10 (87.5%). Our results point to the value of quantitative fluorescence intensity in the flow cytometric evaluation of CD molecular expression or deletion in the diagnosis of hematopathologic disorders, such as plasma cell dyscrasia.
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PMID:Antigenic transformation in plasma cell dyscrasia. 1690 19

The aim of this review is to integrate non-exhaustive relevant data on the phenotype of human plasma cells (PC), including normal, reactive and malignant (multiple myeloma, MM) PC. This review focuses on (i) a universal marker of both normal and malignant plasma cells, CD138; (ii) markers related to malignancy i.e., CD19, CD27, CD28, and CD56; (iii) markers associated with signaling and severity of MM (CD45, CD221). Finally, this review presents data from normal PC up to human myeloma cell lines in order to: (i) define different entities of MM based on expression of CD19, CD20, CD27 and CD117; and (ii) identify new therapeutic targets.
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PMID:The phenotype of normal, reactive and malignant plasma cells. Identification of "many and multiple myelomas" and of new targets for myeloma therapy. 1695 23

CD117 (c-kit) was evaluated on normal plasma cells (PC) (n=10), PC of individuals with monoclonal gammopathy of undetermined significance (MGUS, n=12), malignant PC from patients with multiple myeloma (MM) either at diagnosis (n=83) or relapse (n=38) and on 23 human myeloma cell lines (HMCL). Whereas CD117 is never expressed in normal PC, it is expressed in 50% of MGUS (p=0.015). Furthermore, 33% of MM at diagnosis do express CD117, as opposed to 8% of those in relapse (p=0.003). Finally, CD117 was never found in HMCL. CD117 expression was associated with a better prognosis: overall survival was 93% at 4 years in CD117+ MM versus 64% in CD117- MM (p=0.05). Conversely, lack of CD117, but also high beta-2 microglobulin, t(4;14) and CD221 (IGF-1R) expression were associated with a poorer prognosis. Multivariate analysis revealed that CD117- patients were those with CD221 and t(4;14) and had the poorest prognosis. In conclusion, CD117 (c-kit) is aberrantly expressed on a subset of MGUS and MM with a more indolent presentation and is functionally antinomic to CD221 (IGF-1R). CD117 expression could be related to a specific oncogenic pathway in MM.
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PMID:CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis. 1776 56

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM). Patients may either present de novo (primary PCL), or PCL may occur during the course of MM (secondary PCL). We compared the laboratory and clinical findings of both primary and secondary PCL and MM to elucidate their natural history and the relationship among these entities. Ten cases of PCL (7 cases of primary PCL and 3 cases of secondary PCL) and 20 sex- and age-matched cases of MM were compared. The patients with primary PCL showed significantly lower platelet and neutrophil counts in peripheral blood and higher cellularity in bone marrow than patients with MM (p = 0.002, < 0.001 and 0.027, respectively). Immunophenotypic studies showed a different expression of HLA-DR and CD117 antigens among the 3 groups. There was a significant difference in survival between the 3 groups (median survival of primary PCL, secondary PCL and MM = 22.2, 1.3 and 36.4 months, respectively; p = 0.048). The patients with primary PCL showed better prognosis than those with secondary PCL. Primary PCL might be a differently developed disease from MM. In diagnosing PCL, it is important to differentiate primary PCL from secondary PCL for the prediction of prognosis.
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PMID:Significantly better prognosis for patients with primary plasma cell leukemia than for patients with secondary plasma cell leukemia. 1793 54


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