SignificanceAminoacyl-tRNA synthetases (aaRSs) catalyze aminoacylation of tRNAs in the first step of protein synthesis in the cytoplasm. However, in higher eukaryotes, they acquired additional functions beyond translation. In the present study, we show that an activated form of tyrosyl-tRNA synthetase (YRSACT) functions to enhance megakaryopoiesis and platelet production in vitro and in vivo. These findings were confirmed with human megakaryocytes differentiated from peripheral blood CD34+ hematopoietic stem cells and with human induced pluripotent stem (iPS) cells. The activity of YRSACT is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from iPS cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. These findings demonstrate a previously unrecognized function of an aaRS which may have implications for therapeutic interventions.
Post-transplant lymphoproliferative disorder (PTLD) is a fatal complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is caused by reactivation of Epstein-Barr virus (EBV). A successful approach, monitoring EBV-DNA load in peripheral blood (PB) accompanied by preemptive rituximab therapy, has recently been reported. Here, we describe a 29-year-old woman who developed isolated central nervous system (CNS) PTLD. She received HSCT against acute myelogenous leukemia from a related human leukocyte antigen-haploidentical donor, following a conditioning regimen that included antithymocyte globulin. Tacrolimus and methylprednisolone were given as prophylaxis for graft-versus-host disease. On day +172, the patient's consciousness deteriorated. Magnetic resonance imaging showed six ring-enhanced lesions in the cerebral hemispheres. These tumors were diagnosed, via a craniotomy and tumorectomy, as PTLD. EBV-DNA load was elevated in the cerebrospinal fluid (CSF) but not detected in PB. She was treated with whole-brain irradiation and rituximab, and achieved partial remission of the tumors. This case serves as a reminder that vigilance is required regarding the development of isolated CNS PTLD; it is worth examining EBV-DNA replication in CSF for diagnosis even when the EBV-DNA load is negative in PB.
We describe herein the successful treatment of severe autoimmune hemolytic anemia (AIHA) in a patient with multicentric Castleman disease (MCD) by humanized anti-interleukin-6 (IL-6) receptor antibody (tocilizumab) therapy. Inflammatory anemia is commonly reported; however, AIHA is a very rare complication of MCD. In 1996, a 45-year-old Japanese woman was referred to our hospital because of generalized lymphadenopathy, anemia and skin eruptions. Lymph node biopsy demonstrated MCD. She was treated with prednisolone (1 mg/kg/day), which improved the anemia and skin eruptions. In 2009, she suddenly developed Coombs-positive hemolytic anemia. The blood count was as follows: hemoglobin 4.7 g/dl, platelets 490 × 109/l and white blood cell count 9.8 × 109/l. Both direct and indirect Coombs’ tests were strongly positive. She was treated with 8 mg/kg tocilizumab every 2 weeks. One month later, her hemoglobin levels rose dramatically to 10.9 g/dl and her haptoglobin level, hypergammaglobulinemia and clinical symptoms had also markedly improved. To the best of our knowledge, this is the first report of the efficacy of tocilizumab in AIHA associated with MCD. The well-established role of IL-6 in the pathogenesis of MCD may have been responsible for the improvement in the AIHA associated with MCD. Anti-IL-6 receptor antibody treatment could be an attractive therapeutic approach for AIHA associated with MCD.
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