ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01485.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Monoclonal gammopathies are B lymphocyte‐derived disorders producing a specific monoclonal immunoglobulin. The group includes multiple myeloma, Waldenström's macroglobulinaemia, monoclonal gammopathy of undetermined significance (MGUS) and heavy‐chain disease. In 1% of the cases a double M‐component is present which is referred to as a biclonal gammopathy. The pathogeneses of these disorders are unknown, but several possibly related environmental factors have been identified. In multiple myeloma, an increased incidence and mortality rate has been noted during the last 20 years. Strong lines of evidence are presented showing that, in monoclonal gammopathies, the cell clone consists of B lymphocytes in different stages of maturation. In most cases of biclonal gammopathy there is probably a common cellular

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01486.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

A number of antigens (Ags) are expressed on normal and malignant terminal B (plasma) cells, including plasma‐cell, earlier B‐cell, and non‐B cell‐Ags. These Ags, coupled with indirect and dual fluorochrome labelling techniques, permit characterization of normal and malignant in vitro and in vivo terminal B‐cell differentiation. The majority (90%) of B cells within spleen bear B1 and lack PCA‐1 Ags. As B cells differentiate to pokeweed mitogen in vitro, immunoglobulin (Ig) secretion precedes the appearance of cell surface PCA‐1 and plasmacytoid morphology. Dual fluorescence cell sorting permits characterization of in vivo B‐cell differentiation: B1 + PCA‐1 + cells are more “differentiated” since they are more prevalent in lymph node than spleen, exhibit plasmacytoid morphology and maximal Ig secretion, and no longer respond to triggers of B‐cell proliferation; in contrast, B1 + PCA‐1‐ cells are lymphoid in morphology and may respond to triggers of B‐cell proliferation as “resting” B cells. Similar studies of myeloma cells demonstrated that they may also include cells expressing plasma‐cell, earlier B, and non‐B cell Ags. Although they neither proliferated nor secreted Ig in vitro to G/M‐CSF, G‐CSF, M‐CSF, IL‐1, IL‐1B, IL‐2, or IL‐4, proliferation without Ig secretion (Stimulation Index ≥ 3.0) was induced to IL‐6 in 6 of 10 patients (pts); to IL‐3 (2 pts) and to IL‐5 (2 pts). Myeloma cells which proliferated to the greatest extent to IL‐6 have plasmablast morphology and appear to express an earlier B‐cell phenotype (B4±CALLA±B1 + PCA‐1 ±) than those cells which either did not or only weakly responded (B4‐CALLA ‐B1±PCA ‐1±). Phenotypic definition of growth factor‐responsive myeloma cells may both facilitate their biological characterization in vitr

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01487.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Peripheral blood mononuclear cells (PBMC) from 14 patients with multiple myeloma (MM), 3 patients with benign monoclonal gammopathy, 3 patients with Waldenstrom's macroglobulinaemia (WM) and 2 patients with B‐cell chronic lymphocytic leukemia (B‐CLL) were cultured in vitro in the presence of IL‐3 and IL‐6. After 3 days, actively proliferating immunoblast‐like B cells were apparent in 12/14 cases of MM, 0/3 BMG, 3/3 WM and 0/2 B‐CLL. After 6 d, B blasts had evolved into morphologically evident plasma cells expressing the specific monoclonal light and heavy chains. The data indicate that the concerted action of IL‐3andIL‐6 synergistically promotes the proliferation and differentitation of circulating plasmacell precursors in malignant monoclon

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01488.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Bone marrow plasma cell proliferative activity has been evaluated in a large series of multiple myeloma (MM) patients. This kinetic parameter has been shown to be a useful tool for patient management, and contributes to a correct diagnosis and a selection of high‐risk patients who can be offered high‐dose chemotherapy. The role of ras oncogenes has been evaluated in the pathogenesis of MM. A point‐mutated and activated H‐ras oncogene, introduced in a human lymphoblastoid cell line, was able to induce neoplastic transformation and differentiation to plasma cell. Indeed, mutated alleles of ras genes have been detected in a high percentage of myeloma patients in relapse phase. Phenotypical and functional studies have been carried out in T‐lymphocyte subsets and an impaired cellular immunity has been detected. Such an impairment was related to the disease status: marked alterations were detected in relapse phase, whereas a partial recovery was observed during remiss

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01489.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Cytokines are a group of polypeptide hormones endowed with pleiotropic biological properties. Normal B lymphocytes produce a number of these factors that subserve important regulatory functions in the combined processes of proliferation and differentiation. Also neoplastic B cells can release cytokines and, simultaneously, respond to the same factors in an autocrine circuit that supports their malignant growth. In addition, tumor cells can make use of the factors released by normal cells, either spontaneously or under the influence of inductive signals from the neoplastic cells. Inappropriate or excessive release of cytokines may have an important role in the pathophysiology of some clinical features. Thus, neutralization of cytokine biologic activity in vivo could be a therapeutic strategy for treatment of human B‐cell neoplasia

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01490.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01491.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Mush less is known about the chromosome changes in MM than in other hematological malignancies. The prevalence of abnormal karyotypes is unknown, but there is no evidence for malignant plasma cells or their precursors to have a normal karyotype. The chromosome changes found may be early events, but karyotypic evolution occurs early and rapidly. No specific structural or numerical chromosome anomaly is associated with multiple myeloma or plasma‐cell leukemia. The changes found are those already known to occur in other B‐cell malignancies, particularly B‐CLL and diffuse small cell lymphoma. A 14Q + marker is present in about 30% of all karyotypically abnormal cases, and in 50% of the cases this is due to a t(11;14) (q13;q32). In a minority of cases deletions of 6q are found, and sporadically other B‐cell translocations can be present. Karyotypes are often very complex with numerous structural anomalies involving mainly chromosomes 1, 11 and 17, and numerical anomalies involving chromosomes 3, 7, 9 and 11. Finally, the presence of structural or numerical anomalies of chromosomes 5 and 7 may be heralding or may be indicative of therapy‐induced

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01492.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

B5‐fixed/paraffin‐erabedded Jamshidi needle biopsies from 125 multiple myeloma patients were reviewed according to both morphological and immunohistological criteria. At microscopic examination, the following parameters were evaluated: i) grade of malignancy (low = 56; intermediate = 50; high = 19); ii) growth pattern (interstitial + /‐ sheets/nodules = 90; nodular =13; packed marrow = 18; sarcomatous = 4); III) histological stage (I = 64; II = 35; III = 26). Comparison of the findings in trephine biopsies and aspirates showed that in 30% of the cases the latter led to an understimation of the tumor burden. Immunohistochemical determination of Ig easily allowed: i) differential diagnosis from exuberant reactive plasmacytosis; ii) recognition and counting of neoplastic plasma cells; iii) detection of minimal residual disease after treatment. Immunohistochemistry also confirmed phenotypic aberration of neoplastic plasma cells, showing positivity for CD45, EMA, and cytokeratins in 14%, 59%, and 25% of the cases, respectively. Furthermore, it displayed expression of the P‐glycoprotein in 4/8 resistant cases. These findings underline that routinely processed Jamshidi needle biopsies can be of great value in the study of patients with multiple

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01493.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Renal failure is a common presenting feature in myelomatosis. This review offers a practical means for classifying renal failure in this disease. Three groups are identified: (1) those patients whose renal failure improves or is stable when they are maintained on a high fluid intake; (2) the minority of patients whose renal failure progresses despite high fluid intake; and (3) those patients who are fluid‐intolerant due to oligurlic renal failure or congestive cardiac failure. The difference beween groups 1 and 2 is not simply due to differences in response to chemotherapy, for many group‐1 patients achieve improvement in renal function without or before loss of light chain proteinuria. It is concluded that all patients with myelomatosis with excess monoclonal free light chain proteinuria are at risk from developing renal failure of the type associated with group 1. The chances of them doing so are diminished if they maintain a high fluid intake. Group 2 encompasses a range of conditions not all of which are clearly defined. There is generally a poor correlation between the physical characteristics of light chains and the presence of group‐2 renal fa

ISSN:0902-4441    

DOI:10.1111/j.1600-0609.1989.tb01494.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY