No abstract

Erythropoietin (EPO) stimulates erythroid growth by enhancing the proliferation, maturation and survival of late-stage erythroid progenitor cells. However, the entire process of EPO stimulation remains undetermined. To further clarify the intracellular mechanisms by which EPO affects the growth of erythroid progenitor cells, we analyzed proteins obtained from purified human erythroid colony-forming cells (ECFCs) cultured with or without EPO, and one of the proteins apparently related with EPO stimuli was identified as mortalin (mthsp70/PBP74/Grp75/mot-2), which is a member of the heat shock protein 70 family of chaperones. The amount of mortalin mRNA in ECFCs increased in an EPO dose-dependent manner, and ECFC growth was dependent on the amount of mortalin. Furthermore, expression of mortalin in ECFCs was suppressed by a phosphatidylinositol 3-kinase inhibitor. Finally, we analyzed gene expression patterns in ECFCs cultured with or without EPO after treatment with mortalin small interfering RNA (siRNA) using a DNA microarray. When ECFCs treated with mortalin siRNA were cultured with EPO, the expression of several genes overlapped with the profile seen in control ECFCs cultured without EPO. Our data suggest that mortalin is involved in the mediation of EPO signaling and plays an important role in stimulating the growth of erythroid progenitor cells.

Chronic active Epstein-Barr virus (EBV) infection, which is considered to be a childhood disease, often develops into natural killer (NK) or T-cell lymphoma after recurrent infectious mononucleosis (IM)-

A 20-year-old man with a primary non-seminomatous mediastinal germ cell tumor (yolk sac tumor and immature teratoma) developed hemophagocytic syndrome (HPS) three months after surgical resection. Around the same time, the patient was found to have bone metastases of the germ cell tumor. No other hereditary or acquired diseases related to HPS were found. The thrombocytopenia was refractory to corticosteroid therapy but improved after chemotherapy performed for germ cell tumor progression. Only three cases of germ cell tumor associated with reactive hemophagocytosis have been previously reported. Successful treatment of the present case by chemotherapy for HPS suggests a close relationship between this rare complication and germ cell tumor. 〔J Clin Exp Hematopathol 49(2) : 117-120, 2009〕

The introduction of purine analogs has improved the management of hairy cell leukemia (HCL), [1] but refractory HCL remains difficult to treat. We report the case of a patient with HCL, who was refractory to purine analogs combined with rituximab, but was successfully treated by allogeneic hematopoietic stem cell transplantation (HSCT) and rituximab.A 31-year-old man was referred to our hospital in March 1999 because of bicytopenia: the white blood cell count was 1.5 9 10 9 /L, and the platelet count was 70 9 10 9 /L. There was no peripheral lymphadenopathy, and computed tomography showed mild hepatosplenomegaly. His bone marrow aspirate was hypocellular and infiltrated with morphologically characteristic CD19, CD20, CD25 and CD11c-positive hairy cells (Fig. 1), leading to a diagnosis of HCL. The patient was successfully treated with pentostatin (5 mg/m 2 ) and then cladribine (0.09 mg/kg) until 2002, but in 2004 the leukemic cells became resistant to cladribine. The addition of rituximab to cladribine was not effective. The number of leukemic cells in the bone marrow and peripheral blood increased gradually, and severe neutropenia, lymphopenia and transfusion-dependent thrombocytopenia persisted. In August 2007, the patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-identical brother. The conditioning regimen consisted of 12 Gy total body irradiation and 120 mg/kg cyclophosphamide. The number of infused CD34-positive cells was 5.41 9 10 6 /kg. Cyclosporine A (CsA) and short-term methotrexate (MTX) were used for GVHD prophylaxis.The post-transplant clinical course is shown in Fig. 2. The absolute neutrophil count exceeded 0.5 9 10 9 /L on day 13, and the platelet count became independent of transfusion on day 15. Fever and a skin eruption developed on day 13. Skin biopsy confirmed the diagnosis of grade II acute GVHD, and methylprednisolone (2 mg/kg/day) was started. Although the acute GVHD subsided rapidly, the pancytopenia gradually progressed. On day 21, his bone marrow aspirate was severely hypocellular and still showed residual hairy cells (16.8%), but CD3-positive cells demonstrated complete donor chimerism. To induce a GVL effect, methylprednisolone was rapidly tapered and discontinued on day 40. Although fever and skin eruption due to GVHD recurred on day 39, the pancytopenia remained unchanged, and the bone marrow aspirate revealed an increased proportion of hairy cells (24.7%). Because of severe neutropenia and pulmonary aspergillosis, cytotoxic agents could not be used. Therefore, the patient received weekly doses of rituximab (375 mg/m 2 ) together with methylprednisolone (125 mg) for 4 weeks (on days 50, 57, 64 and 71). After the administration of rituximab, his blood cell count improved rapidly, and the neutrophil and platelet counts had totally normalized on day 73. On day 76, flow cytometry showed that the hairy cells had disappeared from the bone marrow, and complete donor chimerism was confirmed. Skin GVHD reappeared on day 76 and 10 mg of prednisolone wa...