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)

Fifteen patients presenting with plasma cell leukemia (PCL) are reported in detail. The clinicopathologic features of PCL differ from typical myeloma and resemble those of acute leukemia: patients with PCL have less bone disease but a much higher incidence of organomegaly and tissue infiltration as well as diffuse marrow involvement and more pronounced pancytopenia. One of the reported patients developed meningeal plasma cell leukemia and is reported in detail. Cytomorphologic assessment of PCL cells showed nuclear immaturity and obvious nuclear/cytoplasmic asynchrony. Despite the use of cytotoxic agents known to be effective in myeloma, the prognosis in PCL is poor, and the median survival of the reported patients was only 2 mo.
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PMID:Plasma cell leukemia (PCL): A report on 15 patients. 68 31

A case of non-secretory multiple myeloma presenting as primary plasma cell leukaemia in a 65 year old woman is presented. Bone pain was the initial clinical manifestation. Laboratory analysis showed 20% of circulating immature plasma cells. Despite the presence of osteolytic lesions, no M-component could be demonstrated in serum protein electrophoresis, and serum and urine immunoelectrophoresis. Bone marrow aspirate demonstrated an 83% infiltration of plasma cells showing various degrees of immaturity. Immunofluorescence with monoclonal antisera demonstrated intracytoplasmic kappa light chains in a high percentage of plasma cells. Immature plasma cells without cellular capacity to synthesize and excrete complete immunoglobulins could be more aggressive, leading to an initial leukaemic process. Previous work regarding possible pathogenetic mechanisms, clinical and laboratory features, and response to treatment of this extremely rare association are reviewed.
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PMID:Non-secretory multiple myeloma presenting as primary plasma cell leukaemia. 143 33

Myeloma cells obtained from 33 patients were analyzed by electron microscopy to determine whether there is any correlation among ultrastructural characteristics of myeloma cells, drug response, and prognosis. The median survival time after diagnosis of responders (18 cases) and nonresponders (15 cases) was more than 423 days and 139 days, respectively. Nuclear immaturity and three cytoplasmic abnormalities--scattered pattern of mitochondria, single-sac looplike structures, and numerous intramitochondrial granules--were found to be associated with poor outcome. Although the cytoplasm of almost all the myeloma cells examined was judged to be mature or intermediate, the degree of nuclear immaturity was considered to correspond closely to the grade of nuclear-cytoplasmic asynchrony. Thus the electron microscopic examination of myeloma cells is of use to assess accurately their immaturity and abnormality and might provide clues for the prediction of drug response and prognosis of individual patients.
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PMID:Electron microscopic analysis of myeloma cells in relation to drug response and prognosis. 158 99

We investigated the ultrastructure of myeloma cells obtained from four cases of common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma. Clinically, the disease was aggressive and our patients died with a median survival after diagnosis of only 62 days. By light microscopic criteria of Greipp et al., their disease was classified as plasmablastic, immature (two cases), and intermediate. In contrast, the myeloma cells of all four cases were judged to be immature and abnormal on the basis of the electron microscopic observation. Characteristic features were sparse heterochromatin, high to moderate nucleocytoplasmic ratio, nuclear bodies, thin and short rough endoplasmic reticula, scattered pattern of mitochondria, and polysomes consisting of five to six ribosomes, along with irregular nuclear membrane, poorly developed organella, and abnormalities in cytoplasmic structures such as dense bodies, vacuoli, buddings, single-sac loop-like structures, multilamellar bodies, and abnormal inclusion bodies. While overlapping each other, it is suggested that the CALLA-positive and the plasmablastic myelomas should be classified separately. Thus, the electron microscopic study, like the immunological marker analysis, provides a useful means for better assessment regarding immaturity and abnormality of myeloma cells.
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PMID:Ultrastructure of myeloma cells in patients with common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma. 297 35

Twenty-two patients with solitary plasmacytoma of bone (SPB) and 13 with extramedullary plasmacytomas (EMP) were studied. The average follow-up period for SPB was 90 months and 86 months for EMP. Thirty-six percent of patients with SPB developed multiple myeloma (MM) in an average of 39 months, and 23% of patients with EMP developed MM in an average of 23 months. No significant differences in survival, incidence of MM, or interval to the development of MM were found between the two groups. The 11 cases of EMP with evaluable tissue for immunohistochemical study were either monotypic kappa or lambda, as were 9 of 10 SPB. Presence of monoclonality did not predict the development of MM. The histologic parameters of nuclear immaturity and presence of prominent nucleoli seem to be the best indicators of which patients will develop MM. Solitary plasmacytoma of bone and EMP appear to be more closely related than has been previously recognized.
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PMID:Solitary plasmacytomas of bone and extramedullary plasmacytomas. A clinicopathologic and immunohistochemical study. 310 35

Forty-two bone marrow aspirates and biopsies during follow-up examinations from patients with multiple myeloma were reviewed to determine whether the results correlate with the clinical state of the patient at the time of examination. The percentage of plasma cells on biopsy and aspiration, cytological immaturity, patterns of plasma cell infiltration, and the presence or absence of multiple lymphoid nodules and marked fibrosis were cross-tabulated with clinical parameters (hemoglobin levels, osteolytic lesions, and renal function). Hemoglobin levels less than 10 g/dl were more frequent in those with greater than 70% plasma cells on either aspiration or biopsy (P less than 0.05). A nodular histological pattern on biopsy, however, had a higher correlation with hemoglobin levels less than 10 g/dl, and serum creatinine levels greater than 2 mg/dl, than did plasma cell number. The presence of lymphoid nodules correlated with less lytic bone lesions. The degree of fibrosis and plasma cell immaturity did not correlate with any of the clinical parameters. Our findings suggest that reports on bone biopsies should include in addition to the number of plasma cells, the pattern of plasma cell infiltration and the presence or absence of multiple lymphoid nodules.
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PMID:Bone marrow biopsy in multiple myeloma: a clinical pathological study. 340 26

A monoclonal gammopathy (M.G.) is usually associated with multiple myeloma or macroglobulinemia. Cases whose follow up have not demonstrated myeloma or lymphoma for several years are called "benign monoclonal gammopathies" (B.M.G.). Numerous criteria were suggested to distinguish multiple myeloma from B.M.G., chiefly an abnormal medullary plasmacytosis. But frequently it is only beyond 15 to 20 % that this plasmacytosis is considered as significative. Some authors have reported the peculiarities of these plasma cells immune labelling with rather conflicting results. We reviewed semi-thin sections of bone marrow biopsies with a low grade plasmacytosis (less than or equal to 10 %) by histological cytological and immunological methods in a group of 39 patients with a M.G. A diagnosis of multiple myeloma or of B.M.G. was made on the initial examination of these biopsies. The 24 cases of multiple myeloma were diagnosed using : --topographical criteria : inhomogenous sharing, nests of plasmocytes exclusively away from the periphery of vessels, --cytological criteria such as frequent cellular immaturity, nuclear immaturity in binucleated cells, bizarre shaped nuclei . . . --immunological criteria obtained by immunofluorescence method : strictly monoclonal labelling of plasma cells or "limit"-monoclonal labelling in 50 % of cases. The latter is less characteristic because of its presence in 25 % of B.M.G. In this prospective study, the initial diagnosis was maintained in 37 out of the 39 cases according to clinical and laboratory data. These results seem to demonstrate the practical value of the proposed criteria.
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PMID:[Interpretation of minimal medullary plasmacytoses in monoclonal dysglobulinemias. Importance of the study of osteomedullary biopsies of semi-thin sections and immunologic marking]. 676 Aug 76

The development of three novel chemotherapeutic agents - thalidomide, lenalidomide, and bortezomib - has resulted in a fundamental shift in the management of multiple myeloma. Despite this tremendous advancement, the selection of initial treatment must still be made with a degree of uncertainty as a true standard therapy has yet to be established. Although challenging, the relative abundance of therapeutic options, when taken into consideration with unique patient characteristics, creates the potential for individualization of care.For patients eligible for autologous stem cell transplantation, various combinations of novel agents with dexamethasone or traditional chemotherapy have supplanted the previous standard regimen consisting of vincristine, doxorubicin, and dexamethasone. In elderly patients or others that are deemed ineligible for the transplant procedure, the addition of a novel agent to melphalan-prednisone has demonstrated significant improvements in response rates. Due to the immaturity of the available data, it is perhaps best to regard the era of novel agents with a degree of rational enthusiasm, as the ultimate impact on patient care remains undetermined. Although further research is clearly implicated, recent advancements have resulted in significant progress toward obtaining optimum outcomes in a historically challenging disease.
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PMID:Initial therapy in multiple myeloma: investigating the new treatment paradigm. 1927 38

Treatment of multiple myeloma has evolved rapidly over the last decade due to novel therapeutic agents. Improved upfront and salvage options have resulted in enhanced survival; however, this has been less pronounced in elderly patients compared with their younger counterparts. Indeed, treatment-related toxicities in older patients may have subverted the survival benefit made by newer treatment modalities. However, owing to the immaturity of current published data, the true survival impact made by novel agents in the elderly patient subgroup is far from being fully appreciated. Improved responses, along with increased salvage options, imply that progress for elderly patients is being made. The current challenge to improve survival for elderly patients not only rests with continued research into tolerable novel treatment regimens, but also, scrupulous supportive care and the judicious use of current novel agents in appropriate dosing, combinations and sequence. Here, we review the outcomes of elderly patients with multiple myeloma over recent years and focus on the current treatment options available for this group.
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PMID:Managing multiple myeloma in the elderly: are we making progress? 2166 95

The unfolded protein response (UPR) is an essential pathway for both normal and malignant plasma cells to maintain endoplasmic reticulum (ER) homeostasis in response to the large amount of immunoglobulin (Ig) output. The inositol-requiring enzyme 1-X-box binding protein-1 (IRE1-XBP-1) arm of the UPR pathway has been shown to play crucial roles not only in relieving the ER stress by up-regulating a series of genes favoring ER-associated protein degradation and protein folding, but in mediating terminal plasmacytic differentiation and maturation. Myeloma cells comprise various subsets arrested in diverse differentiated phases, and the immaturity of myeloma cells has been taken as a marker for poor prognosis, suggesting that differentiation induction would be a promising therapeutic strategy for myeloma. Herein, we used low-dose pharmacological UPR inducers such as tunicamycin (TM) and dithiothreitol (DTT) to efficiently activate the IRE1-XBP-1 pathway in myeloma cells characterized by transcriptional expression increase in spliced XBP-1 and molecular chaperons, accompanied by significant differentiation and maturation of these myeloma cells, without concomitant cytotoxicity. These differentiated myeloma cells exhibited a more mature appearance with well-developed cytoplasm and a reduced nucleocytoplasmic ratio, and a further differentiated phenotype with markedly increased expression of CD49e together with significantly elevated cellular secretion of Ig light chain as shown by flow cytometry and ELISA, in contrast to the control myeloma cells without exposed to TM or DTT. Moreover, siRNA knockdown of XBP-1 disrupted TM- or DTT-induced myeloma cell differentiation and maturation. Our study, for the first time, validated that the modest activation of the UPR pathway enables myeloma cells to further differentiate, and identified that XBP-1 plays an indispensable role in UPR-mediated myeloma cell differentiation and maturation. Thus, we provided the rationale and feasibility for the exploration of the novel therapeutic strategy of differentiation induction for plasmacytic malignancies.
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PMID:Unfolded protein response inducers tunicamycin and dithiothreitol promote myeloma cell differentiation mediated by XBP-1. 2435 28


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