Publications (90) View all
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Article: Efficient Ex Vivo Generation of Human Dendritic Cells from Mobilized CD34p+ Peripheral Blood Progenitors
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ABSTRACT: We tried to efficiently generate human dendritic cells (DCs) from CD34p+ peripheral blood hematopoietic progenitor cells mobilized by high-dose chemotherapy and subsequent administration of granulocyte colony-stimulating factor, using a liquid suspension culture system. Among various combinations, the combination ofc-kit ligand,flt-3 ligand,c-mpl ligand (TPO), and interleukin (IL)-4 most potently generated the number of CD1ap+CD14p- DCs in cultures containing granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor α (TNF-α). The delayed addition of IL-4 on day 6 of culture gave rise to an additional increase in the yield of CD1ap+CD14p- DCs that were characterized by the expression of HLA-ABC, HLA-DR, CD80, CD86, and CD83. The majority of the sorted CD1ap-CD14p+ cells derived from 6-day culture of CD34p+cells gave rise to CD1ap+CD14p- DCs and CD1a-CD14p+ macrophages on day 12 of culture in the presence and absence of IL-4, respectively. These findings suggest that IL-4 promotes the differentiation of CD1ap-CD14p+ cells derived from mobilized CD34p+ peripheral blood hematopoietic progenitors to CD1ap+CD14p- DCs. The majority of these DCs expressed CD68 but not the Langerhans-associated granule antigen, a finding that suggests they emerge through the monocyte differentiation pathway. The addition of TPO and IL-4 to cultures did not affect the potential of DCs to stimulate the primary allogeneic T-cell response. These findings demonstrated that the combination ofc-kit ligand plusflt-3 ligand plus TPO with GM-CSF plus TNF-α, followed by IL-4, is useful for ex vivo generation of human DCs from mobilized CD34p+ peripheral blood progenitors.International Journal of Hematology 04/2012; 74(3):287-296. · 1.27 Impact Factor -
Article: A potential activity of valproic acid in the stimulation of interleukin-3-mediated megakaryopoiesis and erythropoiesis.
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ABSTRACT: Although the anticancer activities of histone deacetylase (HDAC) inhibitors have been studied, a role for HDAC in normal hematopoiesis has not been clearly defined. Previous studies have shown that the potent HDAC inhibitor FK228 stimulates interleukin (IL)-3-mediated erythropoiesis. Here, we examined whether the widely used valproic acid (VPA) affects megakaryopoiesis as well as erythropoiesis. CD34(+) cells were incubated in serum-free or serum-containing cultures with cytokines, with or without VPA. In the serum-free cultures containing IL-3+stem cell factor (SCF), VPA significantly increased generation of CD61(+)GPA(-) megakaryocytic and a CD61(+)GPA(+) mixture of megakaryocytic and erythroid precursors from CD34(+) hematopoietic precursors at a pharmacological concentration (100 microg/mL). The increase in generation of megakaryocytic and erythroid precursors by VPA was confirmed by replating cultured cells with thrombopoietin+SCF and erythropoietin+SCF, respectively. VPA was as potent as FK228. In cultures with granulocyte-macrophage colony-stimulating factor+SCF, where CD61(-)GPA(+) erythroid precursors were mostly developed, VPA mainly enhanced the generation of CD61(-)GPA(+) erythroid precursors. In serum-containing cultures, only low numbers of CD61(+) or GPA(+) cells were developed with IL-3+SCF. Nevertheless, a substantial number of these cells were generated with VPA. Furthermore, these stimulating effects of VPA were observed by incubating CD34(+) cells from patients with myelodysplastic syndrome. Quantitative reverse transcription polymerase chain reaction showed that VPA enhanced GATA-2, but not GATA-1, messenger RNA expression with IL-3+SCF. These results indicate a novel role for VPA in enhancing the potential of IL-3 to stimulate megakaryopoiesis as well as erythropoiesis and suggest a new therapeutic approach of epigenetic therapy for hematological disease.Experimental hematology 04/2010; 38(8):685-95. · 3.11 Impact Factor -
Article: Correlation between imatinib pharmacokinetics and clinical response in Japanese patients with chronic-phase chronic myeloid leukemia.
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ABSTRACT: Despite the outstanding results generally obtained with imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), some patients show a poor molecular response. To evaluate the relationship between steady-state trough plasma IM concentration (IM-C(min)) and clinical response in CML patients, we integrated data from six independent Japanese studies. Among 254 CML patients, the mean IM-C(min) was 1,010.5 ng/ml. Importantly, IM-C(min) was significantly higher in patients who achieved a major molecular response (MMR) than in those who did not (P = 0.002). Multivariate analysis showed that an MMR was associated with both age (odds ratio (OR) = 0.97 (0.958-0.995); P = 0.0153) and with IM-C(min) (OR = 1.0008 (1.0003-1.0015); P = 0.0044). Given that patients with IM-C(min) values >1,002 ng/ml had a higher probability of achieving an MMR in our large cohort (P = 0.0120), the data suggest that monitoring of IM levels in plasma may improve the efficacy of IM therapy for CML patients.Clinical Pharmacology & Therapeutics 10/2010; 88(6):809-13. · 6.04 Impact Factor -
Article: [Multiple myeloma relapsed or progressed as plasmacytoma after allogeneic reduced-intensity stem cell transplantation: report of three cases].
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ABSTRACT: Autologous peripheral blood stem cell transplantation (auto-PBSCT) is considered the standard therapy for younger patients with multiple myeloma, however, survival curve doesn't reach plateau. On the other hand, allogeneic reduced-intensity stem cell transplantation (RIST) with graft-versus-myeloma (GVM) effects is expected to be the curable therapy. We had three cases received RIST (one case as a salvage therapy for relapse after tandem auto-PBSCT, and two cases as an intentional RIST after achieving partial response by auto-PBSCT). All of three cases relapsing or progressing after RIST showed disease type of plasmacytoma without plasma cells in the bone marrow. That may be because conditioning regimen doesn't include total body irradiation, or GVM is ineffective in plasmacytoma, but effective in bone marrow. Here, we report clinical course of these three cases with some consideration.[Rinshō ketsueki] The Japanese journal of clinical hematology 05/2009; 50(4):289-94. -
Article: [Long-term remission of a nasal NK/T-cell lymphoma patient with massive involvement of the orbita and liver dysfunction].
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ABSTRACT: A 49-year-old woman with high fever and diffuse swelling of the right cheek was referred to our hospital. Computed tomography showed right orbital tumor with massive involvement. Histopathologic examination of the biopsied right orbital tumor demonstrated extranodal NK/T-cell lymphoma, nasal-type. She was treated with six courses of chemotherapy consisting of etoposide and dexamethasone with 50 Gy of concurrent involved-field radiotherapy. Facial swelling and liver dysfunction improved immediately, and after five courses of chemotherapy, she achieved partial remission without any severe adverse events. L-asparaginase was administered in the final course of chemotherapy. There is no evidence of recurrence 56 months after diagnosis.[Rinshō ketsueki] The Japanese journal of clinical hematology 02/2009; 50(1):44-8.
