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

Most human lymphomas remain heterogeneous biologic entities in spite of recent advances in the description of their clinical presentation, cellular morphology, immunophenotype, and genotype. Elucidation of genetic alterations causing malignant transformation may explain pathogenesis, refine differential diagnosis, clarify prognosis, and provide rational basis for new therapy. During the last year the expression of anaplastic lymphoma kinase clarified presentation and provided clues toward the outcome of anaplastic large cell lymphoma; the breakpoints of t(2;5) were mapped; constitutive activation of anaplastic lymphoma kinase by a chromosomal inversion was described; transformation was shown to be independent of nuclear localization of anaplastic lymphoma kinase; and phospholipase C-gamma was identified as a molecular target for the kinase activity of anaplastic lymphoma kinase. Molecular characterization of recurrent chromosome abnormalities has identified new candidate oncogenes: bcl-9, bcl-10, PAX-5, MMSET, and c-maf. Their precise role in malignant transformation, and the frequency of their alteration in lymphoma and myeloma, is not yet defined. The expression of the antiapoptotic protein bcl-2 on aggressive lymphomas was shown to be associated with inferior disease-free survival by several investigators. This may be a target of pharmacologic reduction of bcl-2 levels. Can these advances in molecular pathogenesis improve cure rates for lymphoma? The spectacularly successful molecular modeling of inhibitors for HIV protease suggests that this may be an attainable objective.
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PMID:Recent advances in the molecular pathogenesis of lymphomas. 1050 66

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.
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PMID:Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. 1557 69

AIDS-associated aggressive B-cell lymphomas often have plasmacytoid features. Plasma cell neoplasms in HIV patients were commonly described to have atypical morphology and an aggressive clinical course in the literature. We reviewed 14 cases of neoplasms with marked plasmacytic differentiation in HIV-positive patients to determine their clinicopathologic features. Of these, 13 of 14 had homogeneous morphology and were generally CD45(+), CD20-, PAX-5-, and CD138(+). All were positive for Epstein-Barr virus-encoded RNA (EBER) but lacked EBV late membrane proteins (LMP). Human herpes virus 8 (HHV8) DNA was detected in 6 of 10 cases by nested PCR, but HHV8 latent nuclear antigen (LNA) was absent. The 13 patients ranged in age from 28 to 44 years (median, 41 years) (11 male patients; 2 female patients). All patients had extramedullary and 11 of 13 had extranodal tumor at the initial presentation; 2 had distant marrow involvement. The most commonly involved location was the oral cavity (6 of 13 cases), followed by bone and soft tissue (4 of 13), and the gastrointestinal tract (3 of 13). All 11 patients with follow-up died within 34 months (median, 7 months). The 14th patient who had a nodal disease with more undifferentiated morphology and expression of the HHV8 LNA protein was alive without disease at last follow-up (>72 months), probably representing a novel HHV8(+) lymphoma. We conclude that most plasmacytic tumors in HIV-positive individuals are extramedullary, clinically aggressive EBV(+) tumors identical to plasmablastic lymphoma that does not have the clinical features of plasma cell myeloma.
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PMID:Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm. 1632 36

Cellular biology of primary myeloma cells from myeloma patients, has been rapidly developing by using DNA analysis, gene expression profiling (GEP) and surface marker analysis. These studies reveal that human myeloma cells specifically lose the expression of B cell master gene, PAX-5, and express multi-lineage markers, and XBP-1 transgenic mice showed the late onset of human myeloma-like monoclonal plasmacytosis in the bone marrow of aged mice. GEP reveals that primary myeloma cells are subdivided into 7 groups: among these subgroups, PR (proliferation) group predicts poor prognosis. With regard to molecular mechanism of myeloma oncogenesis, the importance of primary IgH translocation followed by the second IgH translocation is proposed, but it is also noted that human myeloma cells show the marked heterogeneity.
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PMID:[Molecular mechanism of oncogenesis and progression in human myeloma]. 1806 59

Our previous studies demonstrated that a low concentration of 2-methoxyestradiol (2ME2) could induce the differentiation of myeloma cell lines and CD138+ primary myeloma cells from myeloma patients and up-regulate the expression of messenger RNA (mRNA) and protein for the gene encoding X-box binding protein 1 (Xbp-1) in myeloma cell lines. In the present study, we used phosphorothioated antisense oligodeoxynucleotides (ASODN) to investigate the roles and interactions of transcription factors Xbp-1, B-lymphocyte induced maturation protein 1 (Blimp-1), and PAX-5-encoded B-cell-specific activator protein (BSAP), which are thought to be involved in the regulation of B-lymphocytic or plasmacytic differentiation. Blimp-1 ASODN and Xbp-1 ASODN clearly inhibited myeloma cell differentiation and significantly partially inhibited the differentiation effects induced by 2ME2 at low concentration, whereas PAX-5 ASODN clearly induced myeloma cell differentiation and significantly enhanced 2ME2-induced differentiation effects. Moreover, after incubation with Blimp-1 ASODN, the level of Xbp-1 mRNA clearly declined, whereas the level of PAX-5 mRNA significantly increased in myeloma cells. These results demonstrate that transcription factors Xbp-1, Blimp-1, and PAX-5-encoded BSAP play important roles in the regulation of plasmacytic differentiation and exert their effects on differentiation induced by low 2ME2 concentrations. Our primary study provided the rationale for a promising strategy-the future application of transcription-factor ASODN for clinical patients.
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PMID:Transcription factors Xbp-1, Blimp-1, and BSAP are involved in the regulation of plasmacytic differentiation induced by 2-methoxyestradiol in myeloma cell lines. 1819 12