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ABSTRACT: We report a follicular lymphoma (FL) case presenting the coexistence of two tumor cell subpopulations in lymph node (LN) and bone marrow (BM), which exhibited an inverse pattern of immunoglobulin light (IgL) chain gene rearrangement and expression: Igkappa-lambda+ in LN and Igkappa+lambda- in BM. These tumor clones shared an identical BCL2-IgH recombination, accompanying t(14;18)(q32;q21) translocation, and an identical variable, diversity and joining segments joining with clone-specific VH somatic hypermutations on the untranslocated IgH allele. Our study provides further evidence that FL clones, originating from common progenitor cells, can be developed independently at different sites and with different IgL expression after immune selection.
European Journal Of Haematology 03/2009; 82(5):398-403. · 2.61 Impact Factor
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ABSTRACT: The BCL6 gene is frequently disrupted at its 5' noncoding region by 3q27 chromosomal translocations in B-cell lymphoma. As a result of translocation, BCL6 is juxtaposed to reciprocal partners, such as the immunoglobulin (Ig) gene family. Besides the Ig loci, multiple non-Ig partners of the BCL6 translocation have been reported. Here we describe the identification of the GAS5 (growth arrest-specific transcript 5) gene as a novel partner of the BCL6 in a patient with diffuse large B-cell lymphoma, harboring the t(1;3)(q25;q27). In this case, the chromosome 1 breakpoint was located within the intronic small nucleolar RNA (snoRNA) sequence of GAS5 and the chromosome 3 breakpoint at 4 kb upstream of BCL6 exon 1a. As the result of chromosomal translocation, the GAS5-BCL6 chimeric transcripts were expressed, in which the 5'-terminal oligopyrimidine (5'TOP) sequence of GAS5 was fused to the whole coding sequence of BCL6. The GAS5 gene on chromosome 1q25 is the second BCL6 partner, to the SNHG5 on 6q15, which is classified as a non-protein-coding multiple snoRNA host and 5'-TOP class gene.
Cancer Genetics and Cytogenetics 05/2008; 182(2):144-9. · 1.39 Impact Factor
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ABSTRACT: Serum levels of T helper 1 (Th1)/T helper 2 (Th2) cytokines, angiogenic growth factors, and other prognostic factors were measured in 5 young adult patients with virus-associated hemophagocytic syndrome (HPS). Levels of 2 Th1 cytokines (interleukin [IL]-18 and tumor necrosis factor-alpha), 2 Th2 cytokines (IL-10 and IL-6), and 2 angiogenic growth factors (soluble intercellular adhesion molecule-1 and hepatocyte growth factor) were high in all of the patients examined, whereas those of Th1 cytokines such as IL-12 and macrophage inflammatory protein-1a were normal or low. Levels of IL-18 and IL-10 were highest in case 2, with a fatal outcome, and were lowest in case 4, with rapid recovery within 1 month. Although IFN-gamma levels were not elevated in 2 patients (cases 3 and 5), IL-18 levels were markedly high in both of these cases and the IL-6 level was highest in case 3. In contrast with the marked increase in the level of IL-10, the levels of IL-6, sIL-2R, and ferritin decreased rapidly and returned to normal within 2 months after therapy in case 3. The IL-18 level decreased somewhat, but remained elevated for 6 months, and the patient achieved a complete response within 11 months. Taken together, our findings suggest that both IL-18 and IL-10, but not IL-12, may play important roles in young adult patients with HPS via enhancing and suppressing Th1 immune responses, respectively.
Laboratory Hematology 02/2006; 12(2):71-4.
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ABSTRACT: A 39-year-old patient with cervical cancer, stage Ia, was successfully treated by total hysterectomy. Then, after sustained neutropenia for more than 4 years and coincident with its exacerbation, the serum lactate dehydrogenase (LD) level started to elevate and reached a plateau. A test for antineutrophil antibody was negative and LD-3-linked IgAkappa, which may be responsible for high LD activity, was confirmed. The absolute number of blood NK cells was reduced, and a diagnosis of nonimmune chronic idiopathic neutropenia of adult was made. The successive occurrence of these 3 disorders may be based on interrelated immunological abnormalities.
Laboratory Hematology 02/2006; 12(3):148-51.
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Naoki Wakimoto,
Motohiro Misumi,
Tomoya Maeda,
Tsuneyuki Shimada,
Daisuke Wakao,
Yasutaka Sato,
Naoki Takahashi,
Yuichi Sugahara, Katsuhiko Yoshida,
Fumiharu Yagasaki,
Yoshihiro Ito,
Yuichi Nakamura,
Nobutaka Kawai,
Akira Matsuda,
Itsuro Jinnai,
Masami Bessho
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ABSTRACT: A 61-year-old man with primary macroglobulinemia (PMG) had been followed without any treatment as he had no apparent manifestations. After 1 year and 3 months, he was admitted to our hospital with a fever. No signs or symptoms of infection and no progressive increase of serum IgM levels was observed. Non-Hodgkin's lymphoma was not additionally found. Fever without infection, elevated serum LDH level and further enlargement of the spleen compelled us to diagnose his condition as deterioration of the PMG. An immediate fall in his temperature and serum IgM levels was observed after CHOP therapy. Effective therapy must be discussed in the deterioration of this type of disease.
[Rinshō ketsueki] The Japanese journal of clinical hematology 08/2005; 46(7):536-8.
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Naoki Wakimoto,
Motohiro Misumi,
Tomoya Maeda,
Tsuneyuki Shimada,
Daisuke Wakao,
Yasutaka Sato,
Naoki Takahashi,
Yuichi Sugahara, Katsuhiko Yoshida,
Fumiharu Yagasaki,
Yuichi Nakamura,
Nobutaka Kawai,
Akira Matsuda,
Hidekazu Kayano,
Itsuro Jinnai,
Masami Bessho
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ABSTRACT: A 62-year-old woman was admitted to our hospital because of gastric mucosal bleeding. Gastroendoscopy revealed a gastric tumor which was diagnosed from the biopsied specimen as diffuse large B-cell lymphoma (DLBCL). Lymphoma cells had infiltrated the bone marrow showed morphological features resembling Burkitt lymphoma (BL). Nearly 100% of the cells in the bone marrow were positive for MIB-1 immunostaining. The chromosomal study was normal. Surface marker analysis disclosed that the cells were positive for CD10, CD19, CD20 and CD25. As lymphoma cells had infiltrated the central nervous system, combined chemotherapy was performed accompanied with intrathecal administration of anticancer drugs. Although transient improvement was observed, the patient died of the advanced disease three months after admission. As we have shown here, there are some cases of DLBCL with immunohistochemical features resembling BL. Further consideration about the appropriate chemotherapy program for this type of disease might be necessary.
[Rinshō ketsueki] The Japanese journal of clinical hematology 07/2005; 46(6):458-62.
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ABSTRACT: Myelodysplastic syndromes (MDS), especially refractory anemia (RA) are very heterogeneous diseases regarding their morphological, biological and clinical features. One important clinical problem is the difficulty of diagnosis. Soluble transferrin receptors (sTfRs) reflect the erythropoietic activity in the bone marrow (BM). To establish whether determination of serum sTfR could be useful for the differential diagnosis between RA and aplastic anemia (AA), we measured the serum sTfR concentrations, BM cellularity and BM erythroblast percentages in 14 untreated AA and 7 untreated RA patients. The serum sTfR levels of the RA patients (820.1 +/- 402.8 ng/ml) were significantly higher than those of the AA patients (491.1 +/- 195.2 ng/ml; p = 0.0207). However, the serum sTfR values of RA and AA patients also overlapped. A new index, the 'sTfR-E index' [the ratio of serum sTfR level (ng/ml) to BM cellularity (%) x BM erythroblasts (%)] is proposed, which is expected to reflect the number of transferrin receptors (TfR) on the cell membrane per BM erythroblast. The sTfR-E index values of the 7 RA patients (0.395 +/- 0.234) were significantly lower than those of the 14 AA patients (2.669 +/- 1.633; p = 0.0003). The sTfR-E index values of AA and RA patients overlapped only marginally. In conclusion, the sTfR-E index may be a useful new diagnostic tool to distinguish between AA and RA patients.
Acta Haematologica 02/2004; 111(3):138-42. · 1.35 Impact Factor
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British Journal of Haematology 07/2003; 121(5):815-6. · 4.94 Impact Factor
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Katsuhiko Yoshida,
Hidekazu Kayano,
Tsuneyuki Shimada,
Daisuke Wakao,
Naoki Takahashi,
Yuichi Sugahara,
Fumiharu Yagasaki,
Yoshihiro Ito,
Nobutaka Kawai,
Akira Matsuda,
Toshiya Suzuki,
Masami Bessho
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ABSTRACT: A 60-year-old female visited our hospital in May 2001 because of systemic lymphadenopathy. Her white blood cell count was 25,510/microliters with 93% of lymphocytes. Bone marrow aspiration revealed that 86% of nucleated cells were lymphocytes. Lymphocytes in the peripheral blood and bone marrow were positive for CD 5, 19, 20, and sIgx and negative for CD 23. FISH analysis detected the chimeric bcl 1/IgH fusion gene. Immunohistochemistry of a biopsied lymph node revealed that lymphoma cells were positive for cyclin D 1. Mantle cell lymphoma (MCL) was diagnosed at clinical stage IV A. Although a partial remission was obtained after CHOP plus rituximab therapy, the patient's disease recurred in March 2002 and she died in spite of salvage therapy including rituximab. Immunohistochemistry of the bone marrow cells after salvage rituximab therapy revealed that lymphoma cells were still positive for CD 5 and cyclin D 1, but negative for CD 20 and sIgx. We could not exactly determine how frequently CD 20 expression becomes negative in B-cell lymphomas after treatment with rituximab. We found only two reported cases that suggested rituximab down-regulated CD 20 expression in MCL. We herein describe a case of MCL with very notable clinical features.
[Rinshō ketsueki] The Japanese journal of clinical hematology 04/2003; 44(3):174-81.
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ABSTRACT: In our previous study, approximately 60% of aplastic anemia (AA) and refractory anemia (RA) patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEpo) showed a multilineage response. In this study, we analyzed the long-term follow-up of the multilineage responders (multi-R). In the follow-up analysis of 11 multi-R (6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The range of time from the start of treatment to the final contact was 50 to 125 months. Analysis of survival times revealed a significant difference between multi-R and non-multi-R among AA patients given this treatment (P = .016). One AA and 1 RA patient among the multi-R developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients did not need transfusion at final contact. Four of them maintained the target hemoglobin concentration of more than 11 g/dL for quality-of-life benefit. The findings suggested that this result is an important advantage of this treatment.
International Journal of Hematology 11/2002; 76(3):244-50. · 1.27 Impact Factor
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Katsuhiko Yoshida,
Hidekazu Kayano,
Miki Akiba,
Kuniya Kishimoto,
Naoki Takahashi,
Yuichi Sugahara,
Nobutaka Kawai,
Akira Matsuda,
Kunitake Hirashima,
Toshiya Suzuki,
Masami Bessho
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ABSTRACT: A 61-year-old male visited his doctor in October 2000 because of a high fever. Laboratory examination revealed leukocytosis with blast-like cells and thrombocytopenia. He was referred and admitted to our hospital in November 2000. Although he had mild splenomegaly, he had no lymphadenopathy on the first admission. The white blood cell count was 10,520/microliter with 45% blast-like cells and the platelet count was 51 x 10(3)/microliters. Bone marrow aspiration revealed 82% blast-like cells, which were positive for CD5, CD10, CD13, CD19, and CD20. Immunohistochemistry of the bone marrow clot sections revealed blast-like cells were positive for CD5, but negative for TdT, CD23 and cyclin D1. We diagnosed the patient as having de novo CD5-positive diffuse large B-cell lymphoma (DLBCL) with leukemic dissemination. He obtained a complete remission after two courses of CHOP therapy. The third chemotherapy was postponed because of strangulation of the intestine. He relapsed and died in spite of the third chemotherapy. CD5-positive DLBCL is one of the established disease entities that requires an appropriate therapy regimen because it is characterized by elderly onset, extranodal involvement, and a poorer prognosis.
[Rinshō ketsueki] The Japanese journal of clinical hematology 11/2002; 43(10):943-8.
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Ikuo Murohashi, Katsuhiko Yoshida,
Kuniya Kishimoto,
Takashi Takahashi,
Daisuke Wakao,
Itsuro Jinnai,
Fumiharu Yagasaki,
Nobutaka Kawai,
Toshiya Suzuki,
Akira Matsuda,
Kunitake Hirashima,
Masami Bessho
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ABSTRACT: Proliferative response of blast clonogenic cells to various hematopoietic growth factors (HGF), including stem cell factor (SCF) and flt3 ligand (FL) was investigated in 100 patients with acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) in myeloid crisis (MC). The frequency of spontaneous colony formation was significantly high in CML in MC (55%) and AML French-American-British (FAB) subtype M4 (48%) compared with M2 (16%). No spontaneous colony was formed in any of the patients with M1 and M3. The frequency of proliferative response to various HGF alone and in combination according to FAB subtype and CML in MC was as follows: that to granulocyte colony-stimulating factor (G-CSF) was lowest in M1 and CML in MC (50%) compared with other FAB subtypes (>or=86%), that to granulocyte-macrophage CSF (GM-CSF) was lowest in CML in MC (44%) compared with FAB subtypes (>or=74%), and that to interleukin-3 (IL-3) was lowest in CML in MC (30%) compared with FAB subtypes (>or=78%). SCF and FL stimulated blast colony formation in 11% and 17% of patients with M3, respectively, but there was no response to both, and in 60% and 57% of patients with CML in MC, respectively, with 14% showing a response to both. The frequency of proliferative response to both SCF and FL increased in the order of M1 (33%), M2 (63%), M4-5 (95%), and M6 (100%). The results are summarized as follows: absence of spontaneous colony formation and response to HGF other than SCF and FL, designated as HGF-dependent growth (M3); spontaneous colony formation and lowest response to HGF, designated as autonomous growth (CML in MC); and spontaneous colony formation and highest response to HGF including SCF and FL, designated as autocrine growth (M4-6). M1 and M2 were intermediate between CML in MC and M4-6. The relation between in vitro growth pattern of blast clonogenic cells and prognosis in AML FAB subtype and CML in MC is discussed.
Journal of Interferon & Cytokine Research 04/2002; 22(3):335-41. · 3.06 Impact Factor
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Ikuo Murohashi,
Takuya Kashimura,
Kazunori Tominaga,
Daisuke Wakao,
Takashi Takahashi,
Miki Akiba,
Kuniya Kishimoto, Katsuhiko Yoshida,
Fumiharu Yagasaki,
Yoshihiro Itoh,
Tohru Sakata,
Nobutaka Kawai,
Katsurou Itoh,
Toshiya Suzuki,
Akira Matsuda,
Kunitake Hirashima,
Masami Bessho
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ABSTRACT: Mitoxantrone, etoposide and prednisone (MEP)-based regimens using granulocyte colony-stimulating factor (G-CSF) were designed for relapsed and CHOP-resistant diffuse large B-cell lymphomas in a single institution, and the therapeutic effects and adverse reactions were studied. In a total of 49 patients, the MEP regimen had a 41% (9/22) overall response rate compared with 48% (13/27) for the MEP plus carboplatin (C-MEP) regimen (Chi-squared test, P=0.602). Among 38 CHOP-resistant patients, however, the overall response rate to C-MEP [42% (10/24)] was significantly superior compared with MEP [7% (1/14)] (P=0.023), and the overall survival to C-MEP was superior compared with MEP (P=0.088). Taken together, our results, although non-randomized, suggest that a combination of MEP with carboplatin is better than MEP alone in CHOP-resistant diffuse large B-cell lymphomas.
Leukemia Research 04/2002; 26(3):229-34. · 2.92 Impact Factor
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Daisuke Wakao,
Nobutaka Kawai,
Yoshio Kuwayama,
Motohiro Misumi,
Yasutaka Satoh,
Tsuneyuki Shimada,
Miki Akiba,
Kuniya Kishimoto, Katsuhiko Yoshida,
Naoki Wakimoto,
Naoki Takahashi,
Yuichi Sugahara,
Fumiharu Yagasaki,
Yoshihiro Itoh,
Tohru Sakata,
Toshiya Suzuki,
Akira Matsuda,
Masami Bessho
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ABSTRACT: Systemic capillary leak syndrome (SCLS) is a disorder characterized by hypotension, edema, and an increased hematocrit (Ht) due to sudden leakage of plasma into the extravascular space through some unknown mechanism, in which monoclonal gammopathy is observed. A 30-year-old man visited our emergency department because of abdominal pain, and was admitted to our hematology department because of a markedly increased hemoglobin concentration reaching 26.2 g/dl. The polycythemia was thought to be pseudo-polycythemia due to hemoconcentration, and we diagnosed the patient as having SCLS based on the triad of increased hematocrit, whole-body edema which was especially marked in the lower extremities, and monoclonal gammopathy. The patient recovered after administration of extracellular fluids and albumin, but the attacks recurred. Prophylaxis with terbutaline sulfate, theophylline and corticosteroid reduced the frequency of severe attacks. Because there is possibility that patients with SCLS may be admitted to hematology departments due to severe erythrocytosis, we report this case to increase the awareness of hematologists that SCLS is one of the important differential diagnoses of erythrocytosis.
[Rinshō ketsueki] The Japanese journal of clinical hematology 03/2002; 43(2):122-7.
