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| 1.
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Nishiyama, Yoshiaki ; NiShiyama, Nobuaki
概要:
Very recently, we proposed an ordinary differential equation model incorporating promotion of regulatory T cell (Tregs) expansion by leukemic cells, which describes co-evolutional dynamics between leukemic and immune cells in
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progression of acute myeloid leukemia (AML). To evaluate the ability of our model to predict effectiveness of immunotherapy for AML, we performed Monte Carlo simulation of trajectories in phase plane and generated relapse free survival (RFS) curves, which could be compared with clinical data. The resulting RFS curves were in good accordance with clinical outcomes reported in immunotherapies of NK cells infusion with/without Tregs depletion. In addition, our simulation results focusing on consecutive cycles of cell infusion with/without cell depletion qualitatively accounts for the effectiveness of corresponding clinical immunotherapy. The present results suggest that our model may provide valuable information for future design of immunotherapy in AML.
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| 2.
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藤嶋, ゆみえ ; 大竹, 茂樹 ; 竹本, 賢一
概要:
近年、これまで予後中間群とされてきた正常核型の急性骨髄性白血病（AML）が、いく つかの遺伝子変異の有無により予後の予測ができることが明らかになってきた。この遺伝 子変異の中でもnucleophosmin（NPM）、fms-like tyr
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osine kinase receptor-3（FLT3）、 CCAAT/enhancer－binding protein－ （CEBPA）遺伝子変異が重要視されている。本研 究ではサンプルとして骨髄および末梢血分離細胞から抽出、調整したcDNAとgenomic DNAのみならず、これらの塗抹保存標本から抽出したgenomic DNAを用い、PCR-Gene Scan法によってNPM、FLT3およびCEBPA遺伝子変異の同時検出法の実用化を試みた。 プライマーを異なる蛍光色素で標識し、また異なる大きさのPCR産物ができるように設計 すると、多種類の遺伝子変異を同時に検出することが確認できた。しかしながら、その感 度は白血病細胞が10％程度以上存在することが必要であった。この検査法を用いれば、簡 便かつ迅速に白血病の遺伝子検査を実施することができるので、臨床検査法として病院検 査部の業務として採用できるようにさらに精度の検討を行っていくことが必要と考えられ た。【Aim】Nucleophosmin (NPM), internal tandem duplications in the fms-related tyrosine kinase 3 (FLT3-ITD) and CCAAT/enhancer-binding protein- (CEBPA) gene mutations have recently attracted considerable attention in acute myeloid leukemia (AML) with normal karyotype. We investigated the method that can easily and simultaneously detect these aberrations. 【Method】Genomic DNA specimens were collected from not only fresh bone marrow or peripheral blood cells but also smears of these samples. We also extracted and synthesized cDNA from these fresh cells. In all samples, presence of NPM, FLT3 and CEBPA gene mutations were examined by multiplex PCR assay using several colored fluorescence labeled primers, followed by capillary electrophoresis using ABI Prism 310 Genetic Analyzer. In order to easily discriminate gene mutations, we used primers that could amplify PCR products of different size. Abnormal profiles of NPM were confirmed by direct sequencing. 【Result】Ten (20%) NPM and 7 (14%) FLT3-ITD mutations were detected in 49 AML patients. One (2.0%) TAD 1, 15 (30.6%) TAD 2 and none bZIP mutations of CEBPA could be detected in these patients. In analysis of sensitivity, leukemic cells had to be present more than 10% in original sample. This PCR-Gene Scan method is easily and rapidly performed. We suggest that these assays may be introduced in routine analysis of genetic alterations in AML in hospital laboratory after closer examination of accuracy. More samples from uniformly treated patients should be collected to analyze the relationship between these aberrations and the prognosis of them.<br />[原著:Originals]
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| 3.
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Ishiyama, Ken ; Takami, Akiyoshi ; Kanda, Yoshinobu ; Nakao, Shinji ; Hidaka, Michihiro ; Maeda, Tetsuo ; Naoe, Tomoki ; Taniguchi, Shuichi ; Kawa, Keisei ; Nagamura, Tokiko ; Tabuchi, Ken ; Atsuta, Yoshiko ; Sakamaki, Hisashi
概要:
We have recently reported that the outcome of acute myeloid leukemia (AML) patients with t(6;9)(p23;q34) who underwent a
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llogeneic hematopoietic stem cell transplantation (allo-HSCT) was comparable to that of patients with a normal karyotype. We performed a further analysis regarding the prognostic factors for t(6;9)(p23;q34) AML patients who underwent a HSCT. Seven pediatric patients and 57 adult patients, transplanted between 1996 and 2007, were assessed in this study. The overall survival (OS) of the pediatric patients tended to be better than the OS of the adults, although there were no statistically significant differences. The present study focused on the adult patients revealed that the disease status at HSCT was the sole prognostic factor affecting the OS identified in the univariate analysis. A multivariate analysis showed that the disease status at HSCT and M2 in the FAB classification were extracted as the significant variables affecting the OS. The patients who were not in remission at HSCT and had non-FAB-M2 showed a poorer outcome; 6 deaths in the 9 patients were due to a relapse of the AML. These findings suggest that novel therapeutic approaches might be needed for patients with these poor prognostic factors.<br />発行後6か月より全文公開
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Ishiyama, Ken ; Takami, Akiyoshi ; Kanda, Yoshinobu ; Nakao, Shinji ; Hidaka, Michihiro ; Maeda, Tetsuo ; Naoe, Tomoki ; Taniguchi, Shuichi ; Kawa, Keisei ; Nagamura, Tokiko ; Atsuta, Yoshiko ; Sakamaki, Hisashi
概要:
Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor prognosis treated with chemotherapy and a
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utotransplantation. The presence of this karyotype is an indicator for allogeneic hematopoietic stem cell transplantation (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains unclear. We conducted a matched-pair analysis of de novo AML patients with and without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry. A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and 2007, and 171 of 2056 normal karyotype patients matched for age, disease status at HSCT and graft source were selected. The overall survival, disease-free survival, cumulative incidence of relapse and the non-relapse mortality in t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients. A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on the overall survival. These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor. © 2012 Macmillan Publishers Limited All rights reserved.
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| 5.
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Hosokawa, Kohei ; Yamazaki, Hiroto ; Mochizuki, K. ; Ohata, K. ; Ishiyama, K. ; Hayashi, Tomoe ; Kondo, Y. ; Sugimori, Naomi ; Okumura, H. ; Takami, Akiyoshi ; Nakao, Shinji
概要:
Trichosporon fungemia is a rare and fatal fungal infection that occurs in patients with prolonged neutropenia associated with hematologic malignancies. A 21-year-old male developed Trichosporon fungemia during remission induction
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therapy for acute myeloid leukemia (AML). Although two courses of induction therapy failed to induce a remission of AML, combination therapy with voriconazole and liposomal amphotericin B (L-AmB) followed by monocyte colony-stimulating factor ameliorated the Trichosporon fungemia and enabled the patient to receive reduced-intensity bone marrow transplantation (BMT) from his human leukocyte antigen-A one-locus mismatched mother. The patient achieved a durable remission after BMT without exacerbation of Trichosporon fungemia. The combination therapy with voriconazole and L-AmB may therefore be useful in controlling Trichosporon fungemia associated with prolonged neutropenia after remission induction therapy for AML.
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| 6.
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石山, 謙 ; Ishiyama, Ken
概要:
初発急性骨髄白血病に対する標準治療は確立され、高い完全寛解率が得られているが、長期予後については未だに満足ができるものではない。その改善には造血幹細胞移植が必要である。しかし、同種移植では高い移植関連死亡率が問題となるため、移植適応の決定に
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際しては過去のデータに基づいて慎重に判断する必要がある。 The standard treatment for de novo acute myeloid leukemia (AML) has been established. Although patients with AML achieve complete remission at high rates, the long-term prognosis for such patients remains unsatisfactory. It is therefore necessary to perform hematopoietic stem cell transplantation (HSCT) to improve their prognoses, however, a high rate of transplant-related mortality continues to be a problem associated with allogeneic HSCT. We therefore need to carefully determine the indications to safely perform HSCT based on historical data.<br />出版者照会後に全文公開
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