[Acute promyelocytic leukemia recurrence diagnosed due to granulocytic sarcoma of the external auditory canal].

A 47-year-old man was diagnosed with acute promyelocytic leukemia (APL) accompanied by pancytopenia and left forearm swelling. Complete remission was achieved with remission induction therapy using all-trans retinoic acid (ATRA), and consolidation therapy was completed. Three months after the treatment, left ear closure was observed, and a mass lesion was found in the left external auditory canal.

[Successful treatment with rituximab in a patient with refractory thrombotic thrombocytopenic purpura refractory to plasma exchange].

We report a patient with refractory idiopathic thrombotic thrombocytopenic purpura (TTP) who was successfully treated with rituximab. A 50-year-old woman was referred to our hospital with progressive psychoneurotic symptoms, hemolytic anemia and thrombocytopenia. The diagnosis of TTP was confirmed by the absence of ADAMTS13 activity with the presence of circulating ADAMTS13 inhibitor.

Human hematopoietic stem cells can survive in vitro for several months.

We previously reported that long-lasting in vitro hematopoiesis could be achieved using the cells differentiated from primate embryonic stem (ES) cells. Thus, we speculated that hematopoietic stem cells differentiated from ES cells could sustain long-lasting in vitro hematopoiesis. To test this hypothesis, we investigated whether human hematopoietic stem cells could similarly sustain long-lasting in vitro hematopoiesis in the same culture system.

A phase II, open-label, sequential-cohort, dose-escalation study of romiplostim in Japanese patients with chronic immune thrombocytopenic purpura.

This phase II, multicenter, open-label, sequential-cohort, dose-escalation study was designed to evaluate the safety and efficacy of romiplostim, a novel peptibody that increases platelet production, in Japanese patients with chronic immune thrombocytopenic purpura (ITP). Sequential cohorts of four patients each received romiplostim (1, 3, or 6 microg/kg) subcutaneously on days 1 and 8 of the dose-escalation phase. Patients who achieved platelet responses (doubling of baseline platelet counts to > or =50 x 10(9)/L) continued romiplostim weekly during the treatment-continuation phase.

A new red fluorescent protein that allows efficient marking of murine hematopoietic stem cells.

Background: Genetic marking of hematopoietic stem cells (HSCs) with multiple fluorescent proteins (FPs) would allow analysis of their features, including interaction with adjacent cells. However, there are few red FPs that are comparable to green FPs in terms of low toxicity and high fluorescent intensity. This study has evaluated the usefulness of Kusabira Orange (KO) originated from the coral stone Fungia concinna as a red FP for marking of HSCs

Methods: A vector used was the MSCV-type retroviral vector, D Delta Nsap that has the PCC4 cell-passaged myeloproliferative sarcoma virus derived long terminal repeat devoid of a binding site for YY1 and the primer-binding site derived from the dl587rev, respectively.

Detection of the STAT5B-RARA fusion transcript in acute promyelocytic leukemia with the normal chromosome 17 on G-banding.

Acute promyelocytic leukemia (APL) is characterized by chromosomal rearrangements of 17q21, leading to fusion of the gene-encoding retinoic acid receptor alpha (RARA) with a number of alternative partner genes. Signal transducer and activator of transcription 5 beta (STAT5B) is one of the alternative partners. We report a rare case of APL with STAT5B-RARA fusion transcript and the normal chromosome 17 on G-banding.

Repression via the GATA box is essential for tissue-specific erythropoietin gene expression.

In response to anemia, erythropoietin (Epo) gene transcription is markedly induced in the kidney and liver. To elucidate how Epo gene expression is regulated in vivo, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of a 180-kb mouse Epo gene locus. GFP expression was induced by anemia or hypoxia specifically in peritubular interstitial cells of the kidney and hepatocytes surrounding the central vein.

Lipocalin 2-mediated growth suppression is evident in human erythroid and monocyte/macrophage lineage cells.

Lipocalin 2 (LCN2), a secreted protein of the lipocalin family, induces apoptosis in some types of cells and inhibits bacterial growth by sequestration of the iron-laden bacterial siderophore. We have recently reported that LCN2 inhibits the production of red blood cells in the mouse. Here we analyzed the role of LCN2 in human hematopoiesis.

Human umbilical cord-derived cells can often serve as feeder cells to maintain primate embryonic stem cells in a state capable of producing hematopoietic cells.

Clinical application of human embryonic stem (ES) cells will require the establishment of methods for their culture, either in the presence or absence of human-derived feeder cells. We have tested the ability of non-immortalized cultured cells derived from human umbilical cord (HUC cells) to support ES cell culture. A primate ES cell line that had been established and maintained with mouse embryonic fibroblasts was cultured on HUC cells for >3 months (HUC-maintained ES cells).

L-arginine administration reverses anemia associated with renal disease.

Recombinant human erythropoietin (rhEpo) has proved to be remarkably safe and effective for the treatment of anemia. Despite the use of rhEpo, concerns about its cost, the need for frequent parenteral administration, and the development of anti-Epo antibodies have prompted the development of improved agents to rescue anemia. Patients with anemia associated with renal disease are usually treated by intravenous or subcutaneous rhEpo administration; however, some patients do not respond well to rhEpo, because of the presence of Epo antibody or other unknown reasons.

An immunotherapy approach with dendritic cells genetically modified to express the tumor-associated antigen, HER2.

Dendritic cells (DC), genetically modified to express ovalbumin by the retroviral vector GCDNsap, can elicit stronger anti-tumor immunity than those loaded with the peptides. To assess the clinical feasibility of the strategy, such DC were prepared by differentiation of hematopoietic progenitor cells transduced with the human epidermal growth factor receptor 2 (HER2). When inoculated in mice, the DC primed both HER2-specific cytotoxic T lymphocytes and type 1 T helper lymphocytes, resulting in production of HER2-specific antibody.

Identification of a novel fusion gene MLL-MAML2 in secondary acute myelogenous leukemia and myelodysplastic syndrome with inv(11)(q21q23).

We have identified a novel fusion partner of MLL, namely the mastermind like 2 (MAML2 gene), in secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with inv(11)(q21q23). RT-PCR and sequencing revealed that exon 7 of MLL was fused to exon 2 of MAML2 in the AML and MDS cells. The inv(11)(q21q23) results in the creation of a chimeric RNA encoding a putative fusion protein containing 1,408 amino acids from the NH2-terminal part of MLL and 952 amino acids from the COOH-terminal part of MAML2.

Development-dependent expression of cyclin D3 in precursor T-cell lymphoblastic leukemia/lymphoma.

In contrast to the clear oncogenic role of cyclins D1 and D2, cyclin D3 is suggested to have a role in the initiation and/or maintenance of differentiation in a lineage-associated manner in addition to its basic role in proliferation. Recently, it has been reported that in cyclin D3-deficient mice, normal expansion of T lymphocytes is impaired because of maturation arrest at the double-negative thymocyte stage, suggesting a crucial role for cyclin D3 in early T-cell development. Therefore, cyclin D3 expression was examined in 36 human precursor T-lymphoblastic leukemia/lymphomas (T-LBLL), a neoplastic counterpart of T cells at the early developmental stages of differentiation.

Involvement of Ku80 in microhomology-mediated end joining for DNA double-strand breaks in vivo.

Mammalian cells have an activity of mutagenic repair for DNA double-strand breaks (DSBs), microhomology-mediated end joining (MMEJ), in which DNA ends are joined via microhomologous sequences flanking the breakpoint. MMEJ has been indicated to be undertaken without Ku proteins, which are essential factors for non-homologous end joining (NHEJ). On the other hand, recent studies with cell-free (in vitro) systems indicated the involvement of Ku proteins in MMEJ, suggesting that MMEJ could be also undertaken by a Ku-dependent pathway.

Quinupristin/dalfopristin and voriconazole controlled Staphylococcus epidermidis pneumonia and chronic necrotizing aspergillosis in a patient with severe lung degradation consequent to multiple treatments for Hodgkin's lymphoma.

We report here a 34-year-old woman with complicated severe opportunistic pulmonary infection, who was treated with the newly developed antibiotics quinupristin/dalfopristin (QPR/DPR) and voriconazole. She had received repeated chemotherapy, irradiation of the left lung, autologous and allogeneic bone marrow transplantation (BMT), and segmentectomy of the base of the left lung as treatments for Hodgkin's lymphoma. Although she had been in complete remission (CR), the structure of the left lung was severely degraded.

Granulocyte colony-stimulating factor prevents progression of monocrotaline-induced pulmonary arterial hypertension in rats.

Background: Regeneration of the lung microvasculature and replacing pulmonary artery lesions with functional endothelial cells could be a novel and effective therapeutic strategy for treating advanced pulmonary arterial hypertension (PAH). In the present study it was postulated that granulocyte colony-stimulating factor (G-CFS), which induces the proliferation of endothelial cells, would stimulate endothelial regeneration in situ at sites of impaired lung vasculature and prevent the development of PAH.

Methods And Results: Daily administration of G-CSF for 48 days did not affect the hemodynamism of normal Fischer 344 rats.

Stable transgene expression in mice generated from retrovirally transduced embryonic stem cells.

Silencing of transduced genes hampers production of transgenic mice using retroviral vectors. We show stable expression of the enhanced green fluorescent protein (EGFP) gene in chimeric mice generated from retrovirally transduced embryonic stem cells. The vector was a murine stem cell virus-typed retroviral vector (GCDsap) in which the long terminal repeat and primer-binding site were derived from a PCC4 cell-passaged myeloproliferative sarcoma virus and the endogenous retrovirus dl587rev, respectively.

Efficient enucleation of erythroblasts differentiated in vitro from hematopoietic stem and progenitor cells.

Erythroblast enucleation is thought to be largely dependent on signals mediated by other cells, such as macrophages. In an attempt to improve the in vitro production of red blood cells (RBCs) from immature hematopoietic progenitor cells, we have developed a method to produce enucleated RBCs efficiently in the absence of feeder cells. Our method may represent an efficient way to produce transfusable RBCs on a large scale from hematopoietic progenitors.

Exposure of medical staff to Strongyloides stercolaris from a patient with disseminated strongyloidiasis.

We examined whether medical staff were infected with Strongyloides stercolaris through exposure to the body substances of a patient with disseminated strongyloidiasis. The patient excreted a large number of S. stercolaris organisms in respiratory secretions and stool-like excretions from a nasogastric tube.

Successful treatment of a patient with POEMS syndrome by tandem high-dose chemotherapy with autologous CD34+ purged stem cell rescue.

A 36-year-old man was admitted because of numbness and muscle weakness in the lower extremities. He had gait disturbance, malaise, and body weight loss. Based on the existence of monoclonal gammopathy, the proliferation of abnormal plasma cells in the bone marrow, the presence of sclerotic bone lesion, polycythemia, mild splenomegaly, and an elevated level of serum vascular endothelial growth factor (VEGF) (14,900 pg/mL; normal, 62-707), he was diagnosed as having peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.

2-Oxoglutarate downregulates expression of vascular endothelial growth factor and erythropoietin through decreasing hypoxia-inducible factor-1alpha and inhibits angiogenesis.

In oxygenated cells, hypoxia-inducible factor-1 (HIF-1) alpha subunits are rapidly degraded by a mechanism that involves ubiquitination by the von Hippel-Lindau tumor suppressor E3 ligase complex using 2-oxoglutarate as a substrate. We examined the effect of 2-oxoglutarate on the production of erythropoietin and vascular endothelial growth factor (VEGF). The expression of erythropoietin and VEGF protein were dose-dependently downregulated in Hep3B cells by the addition of 2-oxoglutarate.

Centrosome amplification in adult T-cell leukemia and human T-cell leukemia virus type 1 Tax-induced human T cells.

Centrosomes play pivotal roles in cell polarity, regulation of the cell cycle and chromosomal segregation. Centrosome amplification was recently described as a possible cause of aneuploidy in certain solid tumors and leukemias. ATL is a T-cell malignancy caused by HTLV-1.

Reticulocyte-gated flow cytometric analysis of red blood cells in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by the deficiency of glycosyl phosphatidylinositol (GPI)-anchored proteins in the affected blood cell membranes. Analysis of blood cells by flow cytometry is useful to identify the affected blood cells with PNH-specific phenotypes. Because PNH-affected red blood cells (RBC) have shortened life-spans in the circulation, ratios of PNH-affected populations analyzed by flow cytometry in whole RBC are lower than those in PNH-affected erythropoiesis.