Human B cell stimulatory factor 2 (BSF-2) was originally characterized and isolated as a T cell-derived factor that caused the terminal maturation of activated B cells to immunoglobulin-producing cells. Molecular cloning of the complementary DNA predicts that BSF-2 is a protein of relative molecular mass (Mr) 26,000 similar or identical to interferon beta 2, hybridoma plasmacytoma growth factor and hepatocyte stimulating factor. IL-6 has been proposed as a name for this molecule. It is now known that BSF-2 has a wide variety of biological functions and that its target cells are not restricted to normal B cells. Responses are also seen in T cells, plasmacytomas, hepatocytes, haematopoietic stem cells, fibroblasts and rat phoeochromocytoma, PC12 (Satoh, T. et al., manuscript in preparation). Of particular interest to this report is that human BSF-2 is a potent growth factor for murine plasmacytomas and hybridomas. This observation suggested to us that constitutive expression of BSF-2 or its receptor could be responsible for the generation of human myelomas. In this study we report that myeloma cells freshly isolated from patients produce BSF-2 and express its receptors. Moreover, anti-BSF-2 antibody inhibits the in vitro growth of myeloma cells. This is direct evidence that an autocrine loop is operating in oncogenesis of human myelomas.

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed, refractory, or ineligible, to an IMiD (Immunomodulatory Drug), with measurable disease and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T0). The median age at diagnosis was 58 years and time from diagnosis to T0 was 3.3 years. Following T0, 213 (74%) patients had a treatment recorded with one or more regimens (median=1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (51%) including >=partial response in 69 (38%). The median overall survival and event free survival from T0 were 9 and 5 months respectively. This study confirms the poor outcome once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs.

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In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.

In the search for a more effective adjuvant therapy to treat multiple myeloma (MM), we investigated the effects of the traditional Chinese herbal medicines Huang-Lian-Jie-Du- Tang IntroductionMultiple myeloma (MM) is an incurable plasma-cell malignancy and the second most common hematologic malignancy, with 14 000 new patients diagnosed in the United States annually. 1,2 Although combination chemotherapy offers initial response rates of 40% to 70% in MM patients, 3 refractoriness to these regimens eventually develops. High-dose chemotherapy with stem cell support has achieved higher response rates than conventional therapy, but few patients remain in long-term remission. 4 Thus, the development of a more effective therapy to treat early and advanced MM has become a priority.Many components from herbs have been identified as effective in the treatment of human disease. Curcumin, a major component of turmeric, is able to correct defects associated with the homozygous expression of delta F508 cystic fibrosis 5 and to suppress the growth of myeloma cells. 6 Arsenic trioxide, a compound of arsenic, is very effective in the treatment of patients with acute promyelocytic leukemia who have developed resistance to all-trans retinoic acid (ATRA). 7 Artemisinins, extracted from sweet wormwood, are the most potent antimalarials available, rapidly killing Plasmodium falciparum at all asexual stages by inhibiting the sarcoplasmic or endoplasmic reticulum calcium ATPase (SERCA) ortholog (PfATP6) in Xenopus oocytes with a similar potency to thapsigargin. 8 Consequently, they are widely used to treat multidrug-resistant malaria, a disease that claims 1 million lives annually. 9 Inflammation and MM may be induced partly in the same way, as interleukin 6 (IL-6) is a potential mediator in these conditions. 10,11 Many Kampo medicines have been used historically in anti-inflammatory therapy. By screening the effects of antiinflammatory Kampo formulas on MM cells, we hoped to find one to treat MM. Huang-Lian-Jie-Du-Tang (HLJDT) contains Coptis rhizoma, Phellodendron bark, Scutellaria radix (root), and Gardenia fruit in 2.0, 1.5, 3.0, and 2.0 parts, respectively. It is recognized in Japan and China as an effective anti-inflammatory agent and has been widely used in the treatment of various inflammatory diseases such as gastritis, dermatitis, aphthous stomatitis, and hypertension. HLJDT exhibited anti-inflammatory activity in experimental colitis induced by dextran sulfate sodium, 12 and in animal experiments it inhibited the proliferation of lymphocytes under inflammatory conditions by suppressing the secretion of proinflammatory cytokines including interferon ␣ (IFN-␣) and IFN-␥. 13 The secretion of these cytokines was also reported to be suppressed by HLJDT in is the recipient of a Postdoctoral Fellowship Award for Foreign Researchers (P04500) from the Japan Society for the Promotion of Science (JSPS).Reprints: Michio M. Kawano, Department of Bio-Signal Analysis, AMES, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami-...