chronic myelogenous leukemia (cml) is a stem cell disorder sometimes associated with lymphoproliferative disorders. cml may precede a lymphoproliferative disorder. there are a few reports showing associating of cml with multiple myeloma and we report a known cml case that transformed into a full-blown multiple myeloma. this patient had more than 69% of infiltrating myeloma cells in her bone mar...

BACKGROUND Chromosome translocations involving the immunoglobulin heavy chain gene (IgH) on 14q32 are a seminal event in the pathogenesis of many B-cell malignancies. Since myeloma is a post-germinal center tumor of mature, isotype switched plasma cells, we hypothesized that 14q32 translocations would usually involve IgH switch regions. MATERIALS AND METHODS We analyzed a panel of 21 human my...

PURPOSE CD74 (HLA-DR-associated invariant chain) plays a role in antigen presentation. In addition to its expression on antigen-presenting cells, it is expressed by carcinomas of renal, lung, gastric, and thymic origin and by certain sarcomas. The restricted expression of CD74 by normal tissues and its very rapid internalization make CD74 an attractive therapeutic target for both cancer and imm...

The identification of signaling pathways critical to myeloma growth and progression has yielded an array of novel agents with clinical activity. Multiple myeloma (MM) growth is IL-6 dependent, and IL-6 is secreted in an autocrine/paracrine fashion with signaling via the Ras/Raf/mitogen-activated protein kinase (MAPK) pathway. We hypothesized that combining a Ras pathway inhibitor (lonafarnib, S...

Purpose: Despite the recent advances made in the treatment of multiple myeloma, the disease still remains incurable. The oncolytic potential of reovirus has previously been shown and is currently in phase III clinical trials for solid tumors. We tested the hypothesis that reovirus can successfully target human multiple myeloma in vitro, ex vivo, and in vivowithout affecting human hematopoietic ...

Two key features of myeloma cells are the deregulation of the cell cycle and the dependency on the expression of the BCL2 family of anti-apoptotic proteins. The cell division cycle 7 (CDC7) is an essential S-phase kinase and emerging CDC7 inhibitors are effective in a variety of preclinical cancer models. These compounds also inhibit CDK9 which is relevant for MCL-1 expression. The activity and...

Thalidomide has recently been shown to be useful in the treatment of multiple myeloma and may also be useful in the treatment of other hematological malignancies. We have identified a new derivative of thalidomide, S-3-[3-amino-phthalimido]-glutarimide (S-3APG) with dual activity against B-cell neoplasias. S-3APG was able to directly inhibit the proliferation of myeloma and Burkitt's lymphoma c...

We assessed the expression pattern and clinical relevance of BMPs and related molecules in multiple myeloma (MM). MM bone-marrow samples (n=32) had increased BMP4, BMP6, ACVR1 and ACVR2A, and decreased NOG expression compared with controls (n=15), with BMP6 having the highest sensitivity/specificity. Within MM bone-marrow, the source of BMPs was mainly CD138(+) plasma-cell population, and BMP6 ...

Two new human myeloma cell lines have been established from a 36-year-old woman with refractory IgG kappa multiple myeloma in whom bilateral malignant pleural effusions developed. The malignant plasma cells from each effusion were set up in a liquid culture using an L-15 medium containing catalase, glutathione, selenous acid, ascorbic acid, insulin, transferrin, additional glutamine hydrocortis...

Levamisole has been employed as an immunomodulatory agent in conjunction with 5-fluorouracil in the treatment of colon cancer relapse. At high doses, levamisole has been shown to have both anti-cancer and immunosuppressive activities. In vitro, levamisole has been shown to potentiate the anti-proliferative effect of 5-fluorouracil in several types of tumor cell lines; however, its mechanism of ...