fusion by insertion of 21q into 12p has been previously described, 6 we are the first to report the opposite phenomenon, namely insertion of 12p into 21q, producing the same result.

• B-cell lymphomas with surface nucleolin-Fas complexes are resistant to Fas-mediated apoptosis through decreased ligand binding.• Expression of nucleolin protects mice from a lethal agonistic Fas challenge, whereas a non-Fas binding nucleolin mutant does not.Resistance to Fas-mediated apoptosis is associated with poor cancer outcomes and chemoresistance. To elucidate potential mechanisms of defective Fas signaling, we screened primary lymphoma cell extracts for Fas-associated proteins that would have the potential to regulate Fas signaling. An activation-resistant Fas complex selectively included nucleolin. We confirmed the presence of nucleolin-Fas complexes in B-cell lymphoma cells and primary tissues, and the absence of such complexes in B-lymphocytes from healthy donors. RNA-binding domain 4 and the glycine/arginine-rich domain of nucleolin were essential for its association with IntroductionSurvival of individuals with non-Hodgkin's lymphoma (NHL) has improved with recent advancements in chemotherapy regimens, which now include targeted therapies. Despite these advancements, NHL demonstrates frequent relapses and a high mortality rate (30%). 1The principal source of NHL relapse is the survival and expansion of cells resistant to chemotherapy. Stimulation of Fas, a member of the tumor necrosis factor superfamily of apoptosis receptors, by Fas ligand (FasL)-bearing cells or from within damaged cells is an important mechanism of cell elimination, particularly in the lymphoid system. 2,3 Genetic models featuring Fas-disabling mutations develop autoreactive lymphocytes, arising from ineffective negative selection that results in autoimmune disorders and lymphoma. 4,5 Moreover, cells lacking Fas or Fas-defective cells are resistant to customary doses of chemotherapy and radiation. [6][7][8][9] Further investigations determined that Fas is a key component of responses to radiation and chemotherapy regimens, 6 as several forms of chemotherapy, including genotoxic chemotherapy, induce higher expression levels of Fas and/or FasL in order to effectively eliminate tumor cells. 10,11 However, Fas-resistant NHL cells often express normal levels of wild-type Fas and FasL while remaining resistant to Fas activation. The lack of correlation between Fas levels and sensitivity to Fasmediated apoptosis in lymphoid cancer cells indicates additional modulation of the apoptosis pathway. Investigations into the defects of Fas-mediated apoptosis have shown multiple layers of control over Fas signaling. The signaling is initiated by binding of trimeric FasL complexes to a Fas receptor, which recruits the adaptor molecule FADD and subsequently procaspase-8 through the homologous death domain and death effector domain, respectively, to form the death-inducing signaling complex. 3,12 Formation of this complex promotes cleavage and activation of the initiator caspase-8, resulting in activation of an intricate caspase cascade and cell death.13,14 Each of these signaling stages is subjected to different inhibitory mechanisms aimed at pr...

Summary. Phosphorylation of PTEN (phosphatase and tensin homologue) affects PTEN protein stability and function. In this study, phosphorylated PTEN (pPTEN) was observed in 45 (73AE8%) of 61 cases with acute myeloid leukaemia (AML). Phosphorylation of Akt and its downstream molecules [FKHR; Forkhead (Drosophila) homologue 1; and GSK-3b; glycogen synthase kinase 3 beta] was significantly associated with pPTEN (P < 0AE001). The complete remission rates were not different with respect to pPTEN, but overall survival was significantly shorter in patients with pPTEN (P < 0AE05). Constitutive PTEN phosphorylation may add insight into the molecular pathogenesis of AML, and may be a new parameter for an unfavourable outcome.

Oxidative stress is an imbalance between free radicals and antioxidant molecules that can play an important role in the pathogenesis of iron-deficiency anemia (IDA). The aim of this study was to investigate oxidative status in patients with IDA and alteration of oxidative status after iron treatment. Thirty-three female patients with IDA and 25 healthy controls were included in this study. Oxidant and total antioxidant capacity were determined using free oxygen radicals test and free oxygen radicals defence (Form CR 3000, Callegari, Parma, Italy). Catalase activity was measured by spectrophotometer using a commercially available kit (Bioxytech Catalase-520, OxisResearch, Portland, OR). Oxidant activity in patients with IDA was significantly higher than controls (P<0.05), while total antioxidant and catalase activity were significantly lower (P<0.05). After treatment, oxidant, antioxidant, and catalase activity reached the levels of the control group, and no significant differences were observed among groups (P>0.05). In conclusion, our data indicate that blood reactive oxygen species was lower and total antioxidant and catalase activity were higher after rather than before treatment in patients with IDA. The results of our study support the higher oxidative stress hypothesis in IDA; however, due to the limited number of cases included, more studies may be required to confirm the results.