The CCAAT/enhancer-binding protein b (C/EBPb) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK þ ). Although ALK-mediated C/EBPb transcriptional activation has been reported, C/EBPb mRNA possesses U-and AU-rich domains in its 3 0 -untranslated region (3 0 -UTR) that might be privileged targets for posttranscriptional control in ALK þ ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3 0

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Summary. We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day 121; bone marrow showed mixed chimaerism from day 121 to day 1221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.

RK et al. Patterned CpG methylation of silenced B cell gene promoters in classical Hodgkin lymphoma-derived and primary effusion lymphoma cell lines.

We report an unusual case of cerebral toxoplasmosis associated with Guillain-Barré syndrome (GBS) in a 25-year-old patient diagnosed with chronic myelogenous leukaemia (CML), who underwent a mismatched allogeneic peripheral stem cell transplantation (PSCT). On day +83 he started with fever, and 7 days later tremor, muscular weakness, diplopia, dysarthria, respiratory difficulty, and universal arreflexia appeared, compatible with GBS. As the patient had a positive cytomegalovirus (CMV) antigenemia, this was the aetiology suspected for his neurologic findings, but specific treatment failed to improve his clinical situation, and he died on day +123. Necropsy demonstrated cerebral toxoplasmosis and axonal degeneration of nerve roots compatible with the axonal form of GBS. Interestingly, the polymerase chain reaction (PCR) signal for Toxoplasma gondii in two different cerebrospinal fluid (CSF) samples had been negative. In addition, this case showed unique magnetic resonance imaging (MRI) abnormalities. We conclude that a negative PCR on CSF cannot exclude toxoplasmosis in a transplant patient, and we emphasise the importance of considering Toxoplasma as an aetiology of fever and neurological symptoms in the transplant setting.

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<p>Supplementary Figures S1-S3; Supplementary Table S1.</p>

<div>Abstract<p>The CCAAT/enhancer-binding protein <i>β</i> (C/EBPβ) plays a major role in the pathogenesis of anaplastic large cell lymphomas (ALCL) that express the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) tyrosine kinase (ALK⁺). Although ALK-mediated <i>C/EBPβ</i> transcriptional activation has been reported, <i>C/EBPβ</i> mRNA possesses U- and AU-rich domains in its 3′-untranslated region (3′-UTR) that might be privileged targets for posttranscriptional control in ALK⁺ ALCLs. The purpose of this study was to explore this possibility. By using human ALCL-derived cells and a murine model of ALK-transformed cells, we show that the AU-binding protein HuR binds to the 3′-UTR of <i>C/EBPβ</i> mRNA, as previously reported in adipocytes, and that NPM-ALK enhances this interaction. Interaction between HuR and <i>C/EBPβ</i> mRNA impacts on <i>C/EBPβ</i> gene expression at both the mRNA and protein levels. Indeed, <i>C/EBPβ</i> mRNA stability following HuR silencing is reduced and reaches the value observed in ALK-inactivated cells. Remarkably, HuR expression is not modified by NPM-ALK, but its association with actively translating polysomes is dramatically increased in ALK⁺ cells. HuR/polysomes association diminishes when NPM-ALK activity is inhibited and is accompanied by a concomitant decrease of <i>C/EBPβ</i> mRNA translation. Finally, we show that HuR and NPM-ALK colocalized in cytoplasmic granules and HuR is phosphroylated on tyrosine residues in ALK⁺ ALCL cells. Our study thus demonstrates that <i>C/EBPβ</i> is indeed regulated at the posttranscriptional level by HuR in ALK⁺ cells, leading us to propose that part of NPM-ALK oncogenic properties relies on its ability to modify HuR properties in the cytoplasm and hence to alter expression of key actors of transformation. <i>Mol Cancer Res; 9(4); 485–96. ©2011 AACR</i>.</p></div>