Induction of apoptosis in cancer cells of pre-B All patients after exposure to platelets, platelet-derived microparticles and soluble CD40 ligand

Objective: The in vitro treatment of tumor cells with platelet [Plt] causes inhibition of tumor cell growth, although mechanism of this effect is not clear yet. Induction of apoptosis has been proposed as a mechanism of Plt effects on tumor cells. The purpose of this study was to clarify the role of Plts and Plt-derived components in the induction of apoptosis in the blood mononuclear cells of patients with leukemia

Materials and Methods: In this experimental study, peripheral blood mononuclear cells [PBMCs] were isolated from whole blood of five patients with childhood B-precursor acute lymphoblastic leukemia [pre-B ALL] and encountered with Plts, Plt-derived microparticles [Plt-MPs] as well as purified soluble CD40L [sCD40L]. After 48 hours of co-culture, the anti-cancer activity of the aforementioned factors was surveyed using examination of apoptosis markers of the cells including active caspase-3 and CD95 using ELISA and flow cytometer techniques, respectively. Additionally, staining of the cells with 7-Aminoactinomycin D [7-AAD] was evaluated by flow cytometer technique. Trypan blue exclusion test and WST-1 method were also used to compare the death/survival status of the cells

Results: Levels of CD95 and caspase-3 were significantly increased in the all treated groups [P<0.05]. On the other hand, trypan blue, 7-AAD and WST-1 methods showed significantly lower number of the live cells in the treated groups [P<0.05]

Conclusion: This study can show the ability of Plts, Plt-MPs and sCD40L for the induction of apoptosis in PBMCs of pre-B-ALL patients. Further studies are necessary to elucidate the different effects of platelets on cancer cells in vitro and in vivo

Expression of hsa-MIR-204, RUNX2, PPAR gamma, and BCL2 in bone marrow derived mesenchymal stem cells from multiple myeloma patients and normal individuals

Objective: Multiple Myeloma [MM] is a heterogeneous cytogenetic disorder in which clonal plasma cells proliferate in the bone marrow [BM] and cause bone destruction. The BM microenvironment plays a crucial role in pathogenesis of this disease, and mesenchymal stem cells [MSCs] are one of the key players. Herein, we propose to investigate the expressions of hsa-MIR-204, runt-related transcription factor 2 [RUNX2], peroxisome proliferator-activated receptor gamma [PPAR gamma], and B-cell lymphoma 2 [BCL2] as factors involved in osteogenesis, adipogenesis, and MSC survival in BM-MSCs from MM patients and normal individuals

Materials and Methods: In this experimental study, we isolated MSCs from BM aspirates of MM patients and healthy donors. Total RNA were extracted before and after co-culture with L363 myeloma cells. Gene expressions of RUNX2, PPAR gamma, BCL2, and hsa-MIR-204 were assessed by quantitive real time polymerase chain reaction [qRT-PCR]

Results: Higher levels of RUNX2, PPAR gamma, and hsa-MIR-204 expressions existed in MM-MSCs compared to normally derived [ND]-MSCs. BCL2 expression decreased in MM-MSCs. We observed different results in the co-culture model

Conclusion: In general, the MM-MSCs gene expression profile differed compared to ND-MSCs. Upregulation of RUNX2, PPAR gamma, and hsa-MIR-204 in MM-MSCs compared to ND-MSCs would result in formation of bone defects. Downregulation of BCL2 would lead to MM-MSC cell death

[Effects of L-asparginase administration on anticoagulant proteins and platelet function in patients with acute lymphoblastic leukemia]

Acute lymphoblastic leukemia is one the most common malignancies in children and adolescents. L-asparginase [L-ASP] is one of the leading medications in treatment of ALL. L.ASP interferes with the synthesis of some coagulation proteins and therefore causing disturbance in normal coagulation. In this study, the effects of L-ASP on anticoagulant proteins [protein C, protein S, and antithrombin III] and platelet function were assessed. This was a before-after study on 41 patients with ALL who refered to Mahak hospital [Tehran, Iran]. Before and after the injection of L.ASP, a bleeding time test was performed based on Ivy method. Protein C and protein S performance was assessed by turbidometry and antithrombin III performance was evaluated by chromogenic method. 48.8% of patients were female. Mean [ +/- SD] of age was 4.0 +/- 7.2. A significant reduction in the mean amount of protein C, antithrombin III and bleeding time was recorded. However, the reduction in protein S was not significant. No patient showed the symptoms of thrombosis. The results of this study showed that L. ASP drug reduced coagulation proteins [except the protein S]. This decrease along with other concomitant genetic factors can lead to thrombosis in some patients with ALL during induction therapy