We report a case of myeloid/natural killer cell precursor acute leukemia. A 68-year-old man was diagnosed as having lymphoma in his neck, and was referred to our department for further examination and treatment. After admission, blastoid-cells appeared and increased rapidly in his peripheral blood. Cell marker analysis revealed that the blastoid-cells expressed CD7, CD56, CD33, and CD34. He was then diagnosed with myeloid/natural killer cell precursor leukemia. This form of leukemia was recently established as a distinct disease entity. Further clinicopathological evaluation and the establishment of treatment are necessary.

Diagnosis of multiple sclerosis (MS) is difficult when the lesion mimics glioma or cerebral enchephalitis. We report a case of pediatric MS initially suspected as brain stem glioma. An 11-year-old boy developed left foot joint pain followed by progressive symptoms such as left arm and leg weakness, dysarthria, paraplegia, and decreased level of consciousness. He subsequently developed respiratory distress requiring endotracheal intubation and mechanical ventilation. Magnetic resonance imaging showed a mass measuring 2 cm in the medulla oblongata. Although this mass was initially suspected as a glioma, the patient's acutely progressive disease course was not consistent with this diagnosis. Open biopsy revealed inflammation and demyelination, but no malignant cells were detected. He was treated with steroid pulse therapy, which showed dramatic effects. Nine months later, he developed another episode characterized by several neurological symptoms, and the diagnosis of MS was clinically confirmed. Open brain stem biopsy is technically demanding, but this case demonstrates that appropriate neurosurgical evaluation can play an important role in diagnosis by ruling out glioma and confirming MS.

Patients affected by primary immunodeficiency (PID) can be cured by allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of HLA-matched donors, however, incidence of HSCT-related complications is observed. Therefore, gene therapy has been developed as a highly desirable alternative treatment for patients lacking suitable donors. Retrovirus-based gene therapy was begun in 1990 for the patients of adenosine deaminase deficiency, followed by X-linked severe combined immunodeficiency, Wiskott-Aldrich syndrome and chronic granulomatous disease. Although treated patients have had excellent immune reconstitution and resolution of ongoing infections, complications such as a lymphoproliferative syndrome and a disappearance of gene-modified cells were observed in some clinical trials. To overcome these, ongoing and upcoming clinical trials use some new strategies. The use of preconditioning chemotherapy makes space in the bone marrow for the gene-treated stem cells and allows engraftment of multi lineage stem/progenitor cells. Self-inactivating vectors in which strong enhancers of long terminal repeat are eliminated may reduce the risk of insertional activation of proto-oncogene resulting in leukemia. These modifications will surely increase the safety and efficacy of stem cell gene therapy for PID.

Autoimmune demyelinating diseases of central nervous system are relatively uncommon in Asian but, when proceeds to chronic state, disabling neurological conditions. Recent advance in developing disease-modifying reagents for chronic stage of multiple sclerosis is not yet satisfactory and new strategies of therapy are waited. Neural stem cells, which exist in the subependyma and the dentate gyrus of hippocampus of the adult mammalian brain, could be utilized to provide myelin-forming oligodendrocytes and restore function. Some drugs, which are used in clinics, exhibit direct effects on adult neural stem cells to enhance their self-renewal capability and survival and to promote oligodendrocyte differentiation. Alternatively, oligodendrocyte precursor cells derived from iPS cells 3an be transplanted to the demyelinating brains, where the cells extensively migrate out to myelinate naked axons.

  Interleukin 1 (IL-1) was initially defined as a factor which is produced by macrophages and exhibits proliferative activity on thymocytes and fibroblasts, B cell activation and endogenous pyrogen activity. Now IL-1 is known to exhibit pleiotropic activities on various cell types and play important roles in the regulation of immune, nervous and endocrine systems, progression of tumor cells, hematopoietic cell proliferation/differentiation and especially in inflammatory diseases. In 1985 I found that IL-1 exhibits cytocidal activity against human melanoma cells. Since then I have been engaged in the research of various aspects of IL-1. This review summarizes current knowledge of IL-1, including our research and beneficial effect of IL-1 blocking on inflammatory diseases.

A 26-year-old woman, who developed ALL when she was eighteen years old, achieved remission after chemotherapy. Her ALL relapsed when she was twenty-two years old. After re-induction therapy, she underwent cord blood transplantation. Her bone marrow examination on the 42nd day revealed a lymphoblast count of 16%. She was observed without any therapy, but her bone marrow blast count continued to be around 6% for three years without any symptoms. The bone marrow blast fraction originated from the cord blood. Surface marker analysis of the blast fraction initially revealed a pattern of hematogones that was CD10 and CD19 positive, but then showed a myeloblast pattern that was CD13 and CD33 positive. AML developed as donor cell leukemia. When blasts appear in the early phase after transplantation and persist, an observation period is necessary with molecular chimerism, morphology, and surface marker analysis of the blast fraction to consider relapse, hematogones, or donor cell leukemia.

Signal transduction, elicited by Wnt-family of secreted proteins, can be classified intoβ-catenin-dependent canonical Wnt signaling and -independent non-canonical Wnt signaling. Non-canonical Wnt signaling contains planar cell polarity (PCP) pathway and Ca (+ +) pathway, which play central roles in developmental morphogenesis, by regulating cellular functions, including cell polarity and cell migration. In this article, we will overview the molecular basis of non-canonical Wnt signaling, with a particular emphasis on the roles of non-canonical Wnt signaling mediated by Wnt5a and its cognate receptors, Ror-family of receptor tyrosine kinases (Ror1, Ror2) , and will introduce up-to-date information on non-canonical Wnt signaling obtained from recent studies about pathological conditions, including cancer progression and chronic inflammation.

We here report a 2-year-old female with relapsed acute myeloid leukemia (AML) with MLL gene rearrangement in the bone marrow and central nervous system. The 3'-RACE (Rapid Amplification of cDNA Ends) method identified the MLLT10 gene as a fusion partner of the MLL gene. The patient was complicated with hemophagocytic lymphohistiocytosis (HLH) and invasive aspergillosis (IPA) after re-induction treatment with FLAG-IDA following etoposide, cytarabine, and mitoxantrone. Although treatment with systemic anti-fungal drugs was effective for IPA, HLH did not improve. We considered tumor-associated HLH to be initiated from leukemic stem cells (LSCs) in the bone marrow niche because reverse transcription-polymerase chain reaction (RT-PCR) analysis of a bone marrow biopsy sample was positive for MLL-MLLT10. Gemtuzumab ozogamicin and sorafenib had no major effect on acquiring complete remission, and the patient died of progressive AML with an exacerbation of HLH and aspergillosis. LSCs are known to be resistant to conventional chemotherapy due to their quiescence in the cell cycle. Novel therapeutic concepts are important to eradicate LSCs in order to cure AML patients.