Little is known about Akt inhibitor the metabolism of lipids and function of lipases in CLL cells. Performing gene expression profiling including B-cell receptor (BCR) stimulation of CLL cells in comparison to healthy donor CD5 + B cells, we found significant overexpression of lipases and phospholipases in CLL cells. In addition, we observed that the recently defined prognostic

factor lipoprotein lipase (LPL) is induced by stimulation of BCR in CLL cells but not in CD5 + normal B cells. CLL cellular lysates exhibited significantly higher lipase activity compared to healthy donor controls. Incubation of primary CLL cells (n = 26) with the lipase inhibitor orlistat resulted in induction of apoptosis, with a halfmaximal dose (IC(50)) of 2.35 mu M. In healthy B cells a significantly higher mean IC(50) of 148.5 mu M of

orlistat was observed, while no apoptosis was induced in healthy peripheral blood mononuclear cells (PBMCs; P < 0.001). Orlistat-mediated cytotoxicity was decreased by BCR stimulation. Finally, the cytotoxic effects of orlistat on primary CLL cells were enhanced by the simultaneous incubation with fludarabine (P = 0.003). In summary, alterations of lipid metabolism are involved in CLL pathogenesis and might represent a novel therapeutic target in CLL.”
“In this open-label randomized clinical trial, HLA-identical sibling-matched hematopoietic stem cells (HSC) were transplanted (non-MSCs group, n = 15) or cotransplanted with mesenchymal BMS202 mouse stem cells (MSCs) (MSCs group, n = 10) in hematologic malignancy patients. The median number of MSCs infused was 3.4 x 10(5) kg(-1) (range, 0.3-15.3 x 10(5) kg(-1)). MSCs infusions were well tolerated. The median time to neutrophil engraftment (absolute neutrophil count

>0.5 x 10(9) l(-1)) was 16 days for MSCs group JIB04 manufacturer and 15 days for non-MSCs group. The median time to platelet engraftment (platelet count >50 x 10(9) l(-1)) was 30 and 27 days, respectively. Grades II-IV acute graft-versus-host disease (GVHD) was observed respectively, in one (11.1%) and eight (53.3%) evaluable patients. Chronic GVHD was found in one (14.3%) and four (28.6%) evaluable patients. The number of patients who relapsed were six (60.0%) and three (20.0%), and the 3-year disease-free survivals were 30.0 and 66.7%, respectively. Thus cotransplantation of MSCs and HSCs may prevent GVHD, but the relapse rate is obviously higher than the control group. We conclude that use of MSCs must be handled with extreme caution before a large-scale clinical trial is performed.”
“In T-cell acute lymphoblastic leukemia (T-ALL) the cardiac homeobox gene NKX2-5 (at 5q35) is variously deregulated by regulatory elements coordinating with BCL11B (at 14q32.2), or the T-cell receptor gene TRD (at 14q11.2), respectively. NKX2-5 is normally expressed in developing spleen and heart, regulating fundamental processes, including differentiation and survival.