Clinical lessons to be learned from patients developing chronic myeloid leukemia while on immunosuppressive therapy after solid organ transplantation: yet another case after orthotopic heart transplantation.

Chronic myeloid leukemia developing after transplantation of solid organs and concomitant immunosuppression is a rare but still significant clinical phenomenon. We here describe an additional case of a 62-year-old male patient developing CML after orthotopic heart transplantation and medication with cyclosporine A, mofetil-mycophenolate, and steroids. Initial antileukemic therapy was imatinib at a standard dose and within 15 months of therapy a complete cytogenetic response was noted.

BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma.

Objectives: The ubiquitin-proteasome system emerged as a new therapeutic target in cancer treatment. The purpose of this study was to elucidate the effects of the novel proteasome inhibitor BSc2118 on t(4;14) positive and negative multiple myeloma (MM) cells and normal peripheral blood mononuclear cells (PBMNC).

Methods: Human MM cell lines OPM-2, RPMI-8226, and U266 and primary MM cells from bone marrow aspirates were exposed to BSc2118.

Decrease in CD4+ T-cell counts in patients with multiple myeloma treated with bortezomib.

Background: Bortezomib is highly effective in multiple myeloma and is widely used in this disease. Recently, an increased incidence of varicella zoster virus (VZV) reactivation was reported in patients with myeloma undergoing bortezomib treatment.

Patients And Methods: We investigated the influence of bortezomib on T-cell subpopulations in 53 patients with myeloma before initiation of bortezomib and during therapy.

Serum levels of total-RANKL in multiple myeloma.

Background: Receptor activator of nuclear factor-kappaB ligand (RANKL) plays a key role in osteoclast activation in myeloma bone disease. The increased expression of RANKL in the bone marrow microenvironment was demonstrated in several studies, but there are only rare data on circulating RANKL levels in patients with multiple myeloma (MM).

Patients And Methods: In the current study, we investigated the clinical significance of serum RANKL levels, using an enzyme-linked immunosorbent assay test that detects both free and osteoprotegerin (OPG)-bound RANKL (total-RANKL, tRANKL) in patients with newly diagnosed MM (n = 93) and monoclonal gammopathy of undetermined significance (MGUS; n = 20) compared with healthy controls (n = 20).

Serum concentrations of DKK-1 correlate with the extent of bone disease in patients with multiple myeloma.

Objectives: Lytic bone disease is a hallmark of multiple myeloma (MM) and is caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast precursors. So far, there is no study showing a significant difference in serum DKK-1 levels in MM patients with or without lytic bone lesions.

Circulating proteasome levels are an independent prognostic factor for survival in multiple myeloma.

The proteasome is a proteolytic complex for intracellular degradation of ubiquitinated proteins which are involved in cell-cycle regulation and apoptosis. A constitutively increased proteasome activity has been found in myeloma cells. We studied circulating proteasome levels and their prognostic significance in sera of 50 control subjects, 20 persons with monoclonal gammopathies of undetermined significance (MGUS), and 141 previously untreated patients with multiple myeloma (MM) by an anti-20S proteasome enzyme-linked immunoabsorbent assay (ELISA).

Angiogenesis in multiple myeloma.

Multiple myeloma (MM) was the first haematological malignancy in which a prognostic relevance of bone marrow microvessel density (MVD) was shown. Myeloma-induced angiogenesis involves either the direct production of angiogenic molecules by myeloma cells or their induction in bone marrow stromal cells or endothelial cells (EC). Recent data demonstrate an increased angiogenic potential and a paracrine stimulatory effect of bone marrow EC on plasma cells (PC) in MM.