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Successful Remission of Evans Syndrome Associated with Graves' Disease by Using Propylthiouracil Monotherapy 査読

Takashi Ushiki, Masayoshi Masuko, Koji Nikkuni, Jun Terukina-Yoshida, Ayako Momotsu-Nanba, Hiroshi Morikawa, Akio Usami, Ichiro Fuse, Ken Toba, Kazue Takai, Yoshifusa Aizawa

INTERNAL MEDICINE 50 ( 6 ) 621 - 625 2011年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

A 46-year-old woman with Graves' disease was admitted for anemia and thrombocytopenia. She had previously been treated with methimazole but she self-discontinued the treatment 6 months prior to admission. She was diagnosed with Evans syndrome associated with Graves' disease and treated with propylthiouracil without corticosteroids, which normalized her thyroglobulin level. Surprisingly, while Evans syndrome is characterized by frequent relapses, this patient has been in remission of Evans syndrome for approximately 4 years. The remission of Evans syndrome associated with Graves' disease in the absence of immunosuppressive therapy suggests that these 2 diseases have a common pathogenetic mechanism.

DOI： 10.2169/internalmedicine.50.4319

Myelodysplastic Syndrome with Ph Negative Monosomy 7 Chromosome following Transient Bone Marrow Dysplasia during Imatinib Treatment for Chronic Myeloid Leukemia 査読

Kaori Karimata, Masayoshi Masuko, Takashi Ushiki, Takashi Kozakai, Yasuhiko Shibasaki, Toshio Yano, Takashi Abe, Masato Moriyama, Ken Toba, Tatsuo Furukawa, Yoshifusa Aizawa

INTERNAL MEDICINE 50 ( 5 ) 481 - 485 2011年

担当区分：責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：JAPAN SOC INTERNAL MEDICINE

We describe a 60-year-old Japanese patient with chronic myeloid leukemia (CML) who developed myelodysplastic syndrome (MDS) with Ph negative monosomy 7 chromosome following transient bone marrow dysplasia during imatinib treatment. Most cases that developed chromosomal abnormality in Ph negative cells during imatinib therapy were reported to have less clinical implications, while rare cases developed MDS/AML. The present case suggested that metaphase karyotype analysis and bone marrow examination should be performed for the long term follow-up under imatinib treatment in cases showing cytopenia. The results also suggested that monosomy 7 in Ph negative cells may be an indicator of a poor prognosis.

DOI： 10.2169/internalmedicine.50.4481

Correlation Between Imatinib Pharmacokinetics and Clinical Response in Japanese Patients With Chronic-Phase Chronic Myeloid Leukemia 査読

N. Takahashi, H. Wakita, M. Miura, S. A. Scott, K. Nishii, M. Masuko, M. Sakai, Y. Maeda, K. Ishige, M. Kashimura, K. Fujikawa, M. Fukazawa, T. Katayama, F. Monma, M. Narita, F. Urase, T. Furukawa, Y. Miyazaki, N. Katayama, K. Sawada

CLINICAL PHARMACOLOGY & THERAPEUTICS 88 ( 6 ) 809 - 813 2010年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

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.

DOI： 10.1038/clpt.2010.186

成熟顆粒球の殆どが病的芽球から分化したt(8;21)を伴うAML(AML with t(8:21) which most of mature granulocytes differentiated from pathological blast)

Kozakai Takashi, Kobayashi Hironori, Ushiki Takashi, Kitajima Toshiki, Higashimura Masutaka, Yano Toshio, Abe Takashi, Masuko Masayoshi, Furukawa Tatsuo, Toba Ken, Aizawa Yoshifusa

臨床血液 51 ( 9 ) 1228 - 1228 2010年9月

Pharmacokinetic and pharmacodynamic analysis of cyclosporine A (CsA) to find the best single time point for the monitoring and adjusting of CsA dose using twice-daily 3-h intravenous infusions in allogeneic hematopoietic stem cell transplantation 査読

Tatsuo Furukawa, Tori Kurasaki-Ida, Masayoshi Masuko, Nobuhiro Tsukada, Kiyoshi Okazuka, Naoko Sato, Toshio Yano, Takashi Abe, Akihito Momoi, Yasuhiko Shibasaki, Masutaka Higashimura, Kaori Karimata, Masato Moriyama, Takashi Kuroha, Jun Takizawa, Ken Toba, Miwako Narita, Ichiro Fuse, Masuhiro Takahashi, Yoshifusa Aizawa

INTERNATIONAL JOURNAL OF HEMATOLOGY 92 ( 1 ) 144 - 151 2010年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Pharmacological study is predictably effective in establishing an optimal monitoring strategy for the usage of cyclosporine A (CsA) to prevent graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation recipients. Pharmacokinetic profiling of 33 recipients administered CsA twice daily by 3-h intravenous infusion revealed that levels peaked 2-3 h after the start of infusion, and an exponential decline of CsA concentrations after the termination of infusion was observed. The correlation between the area under the curve (AUC(0-12)) and CsA concentration at various time points after infusion revealed that C (2) and C (3) correlated best with AUC(0-12) (r (2) = 0.725), while the trough concentration correlated poorly. Ex vivo T cell stimulation followed by intracellular cytokine detection with flow cytometry revealed that the capacity of T cells to produce cytokines upon stimulation was inversely proportional to the CsA concentration, and reached a minimum at about 700 ng/mL with a marginal decrease above this concentration. Extrapolation using the regression equations of this study and the data from our retrospective study leads to the assumption that the dose adjustment of CsA based on maintaining the C (3) concentration above 800 ng/mL may effectively prevent acute GVHD. To confirm this assumption, a prospective clinical study is required.

DOI： 10.1007/s12185-010-0610-0

Noninvasive Tracking of Donor Cell Homing by Near-Infrared Fluorescence Imaging Shortly after Bone Marrow Transplantation 査読

Takashi Ushiki, Shinae Kizaka-Kondoh, Eishi Ashihara, Shotaro Tanaka, Masayoshi Masuko, Hideyo Hirai, Shinya Kimura, Yoshifusa Aizawa, Taira Maekawa, Masahiro Hiraoka

PLOS ONE 5 ( 6 ) 2010年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PUBLIC LIBRARY SCIENCE

Background: Many diseases associated with bone marrow transplantation (BMT) are caused by transplanted hematopoietic cells, and the onset of these diseases occurs after homing of donor cells in the initial phase after BMT. Noninvasive observation of donor cell homing shortly after transplantation is potentially valuable for improving therapeutic outcomes of BMT by diagnosing the early stages of these diseases.
Methodology/Principal Findings: Freshly harvested near-infrared fluorescence-labeled cells were noninvasively observed for 24 h after BMT using a photon counting device to track their homing process. In a congenic BMT model, the homing of Alexa Fluor 750-labeled donor cells in the tibia was detected less than 1 h after BMT. In addition, subsequent cell distribution in an intraBM BMT model was successfully monitored for the first time using this method. In the allogeneic BMT model, T-cell depletion decreased the near-infrared fluorescence (NIRF) signals of the reticuloendothelial system.
Conclusions/Significance: This approach in several murine BMT models revealed that the transplanted cells homed within 24 h after transplantation. NIRF labeling is useful for tracking transplanted cells in the initial phase after BMT, and this approach can contribute to in vivo studies aimed at improving the therapeutic outcomes of BMT.

DOI： 10.1371/journal.pone.0011114

WT1 PEPTIDE VACCINATION IN COMBINATION WITH IMATINIB THERAPY FOR A PATIENT WITH CML IN THE CHRONIC PHASE 査読

Miwako Narita, Masayoshi Masuko, Tohri Kurasaki, Toshiki Kitajima, Shoko Takenouchi, Anri Saitoh, Norihiro Watanabe, Tatsuo Furukawa, Ken Toba, Ichiro Fuse, Yoshifusa Aizawa, Manabu Kawakami, Yoshihiro Oka, Haruo Sugiyama, Masuhiro Takahashi

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 7 ( 2 ) 72 - 81 2010年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：IVYSPRING INT PUBL

Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer(+)CD8(+) CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 10(6) CD8(+) T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.

Induction of antigen-specific cytotoxic T lymphocytes by using monocyte-derived DCs transfected with in vitro-transcribed WT1 or SART1 mRNA 査読

Miwako Narita, Nozomi Tochiki, Anri Saitoh, Norihiro Watanabe, Masami Kaji, Noriyuki Satoh, Akie Yamahira, Takeshi Nakamura, Masayoshi Masuko, Tatsuo Furukawa, Ken Toba, Ichiro Fuse, Yoshifusa Aizawa, Masuhiro Takahashi

MEDICAL ONCOLOGY 26 ( 4 ) 429 - 436 2009年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：HUMANA PRESS INC

To evaluate the usefulness of monocyte-derived dendritic cells transfected with tumor antigen mRNA for dendritic cell-based antitumor immunotherapy, we attempted to generate antigen-specific cytotoxic T cells by priming lymphocytes with monocyte-derived dendritic cells transfected with in vitro-transcribed tumor antigen mRNA. Mature monocyte-derived dendritic cells were generated from microbeads-separated CD14(+) cells by culturing with GM-CSF/IL-4 for 7 days and with TNF-alpha, IL-1 alpha, IL-6, and PGE(2) for the last one day. Monocyte-derived dendritic cells, lymphocytes, and target cells, which were positive for HLA-A24, were used in the present study. Although lymphocytes prestimulated with untransfected monocyte-derived dendritic cells did not possess the cytotoxic ability against the target cells in a (51)Cr-release cytotoxicity assay, lymphocytes primed with tumor antigen RNA-transfected monocyte-derived dendritic cells were cytotoxic against the tumor antigen-expressing cells but not against the target cells without the expression of the antigen. The cytotoxic ability of the lymphocytes was blocked by the addition of antibodies against MHC class I but not by antibodies against MHC class II. These findings revealed that monocyte-derived dendritic cells transfected with WT1 or SART1 mRNA are able to induce tumor antigen-specific cytotoxic T cells and applicable for antitumor dendritic cell-based cellular immunotherapy.

DOI： 10.1007/s12032-008-9142-3

Sequential adenovirus infection of type 14 hemorrhagic cystitis and type 35 generalized infection after cord blood transplantation 査読

Takashi Abe, Tatsuo Furukawa, Masayoshi Masuko, Atsunori Sugimoto, Kiyoshi Okazuka, Keiichiro Honma, Takeo Fujimura, Seitaro Iguchi, Shinichi Nishi, Mitsuhiro Ueno, Masayuki Nagahashi, Gen Watanabe, Yoichi Ajioka, Noriatsu Isahai, Koichi Nagai, Yukumasa Kazuyama, Yosifusa Aizawa

INTERNATIONAL JOURNAL OF HEMATOLOGY 90 ( 3 ) 421 - 425 2009年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

We report a case of a 29-year-old male patient with a generalized adenovirus (AdV) infection after cord blood transplantation (CBT) for acute myelocytic leukemia with maturation at 2nd complete remission. Before engraftment, hemorrhagic cystitis was caused by AdV, which resulted in hydronephrosis, renal failure, and adenoviremia on day 34. Forced diuresis, hemodialysis, withdrawal of cyclosporin A, and administration of gamma-globulin or vidarabine were not effective and the patient died of pulmonary alveolar hemorrhage on day 67. At autopsy, old inflammatory change only was observed in the bladder section. In the lungs and kidneys, granular deposits in the nucleus and a high copy number of AdV-DNA were observed. Molecular diagnosis using PCR-restriction fragment length polymorphism analysis demonstrated that AdV with the serotype 14 caused the cystitis. However, retrospective genome typing using PCR sequencing revealed the infection of AdV serotype 35 in the kidneys, lungs, and serum. The present case suggested that Adv infection could not be always caused by a single AdV serotype, and suggested that multiple serotype infection was very difficult to treat. It is desired that a consensus regarding the treatment of AdV infections is established.

DOI： 10.1007/s12185-009-0416-0

A chronic myeloid leukemia patient with atypical karyotype and BCR-ABL e13a3 transcript caused by complex chromosome rearrangement 査読

Masayoshi Masuko, Tatsuo Furukawa, Takashi Abe, Reiko Wada, Soichi Maruyama, Toshiki Kitajima, Yasuhiko Shibasaki, Ken Toba, Masahiko Okada, Yoshifusa Aizawa

INTERNATIONAL JOURNAL OF HEMATOLOGY 90 ( 2 ) 230 - 234 2009年9月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：SPRINGER TOKYO

Philadelphia (Ph) chromosome as a result of t (9; 22) (q34; q11) is observed in more than 90% of chromic myeloid leukemia (CML) patients. Cases in which the typical Ph chromosome is not visible at the karyotype level comprise 5-10% of CML patients. CML cases with fusion transcripts such as e13a3 in which ABL exon 3 rather than exon 2 has fused to BCR are very rare. Such reported cases with the e13a3 transcript show the Ph chromosome on karyotype analysis. We reported an atypical karyotype CML patient with the e13a3 BCR-ABL transcript caused by complex translocation. Fluorescence in situ hybridization (FISH) analysis of the metaphase led to a precise cytogenetical characterization. The patient showed favorable response to imatinib, and achieved major molecular responses.

DOI： 10.1007/s12185-009-0368-4

Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: retrospective analysis of 73 patients who received cyclosporin A 査読

N. Izumi, T. Furukawa, N. Sato, K. Okazuka, N. Tsukada, T. Abe, T. Yano, T. Kurasaki, M. Masuko, K. Toba, M. Takahashi, Y. Aizawa

BONE MARROW TRANSPLANTATION 40 ( 9 ) 875 - 880 2007年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Cyclosporin A (CsA) has been used most widely as an immunosuppressive agent for preventing graft-versus-host disease (GVHD). To explore the risk factors including CsA blood levels for grades II-IV acute GVHD, we retrospectively analyzed the data of patients who underwent allogeneic hematopoietic stem cell transplantation in our hospital between March 1989 and July 2001. Seventy-three patients ( 47 males and 26 females) received CsA and short-term methotrexate for GVHD prophylaxis. CsA 1.5 mg/kg was administered as a 3-h infusion twice daily from day -1 until the patient recovered from the toxic gastrointestinal complication. Methotrexate was given at a dose of 15 mg/m(2) on day 1 and 10 mg/m2 on days 3, 6 and 11. Grades II-IV acute GVHD occurred in 18 patients ( 24.7%). Multivariate Cox regression analysis revealed that higher C-5 ( the whole-blood CsA concentration at 5 h after the start of infusion) before the onset of acute GVHD reduced the onset of grades II-IV acute GVHD with a hazard ratio of 0.994 (95% confidence interval 0.989-0.999) for every increase of 1 ng/ml. Our data indicate that inadequate exposures of CsA can be a vital risk for developing acute GVHD. From our results, we consider that precise monitoring of CsA concentrations and adjustment of CsA dose using the concentration may be effective to prevent the onset of severe acute GVHD. To confirm this finding, further prospective study will be needed.

DOI： 10.1038/sj.bmt.1705834

Successful all-trans retinoic acid treatment of acute promyelocytic leukemia in a patient with NPM/RAR fusion 査読

Kiyoshi Okazuka, Masayoshi Masuko, Yoshinobu Seki, Hitomi Hama, Noriyuki Honma, Tatsuo Furukawa, Ken Toba, Kenji Kishi, Yoshifusa Aizawa

INTERNATIONAL JOURNAL OF HEMATOLOGY 86 ( 3 ) 246 - 249 2007年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：CARDEN JENNINGS PUBL CO LTD

Acute promyelocytic leukemia (APL) is characterized by a reciprocal chromosomal translocation involving the gene for retinoic acid receptor alpha (RAR). Most APL patients have a t(15;17) translocation that generates the PML-RAR fusion gene, and such patients respond well to treatment with all-trans retinoic acid (ATRA). Some APL cases also involve rearrangements that fuse RAR to partner genes other than PML, including nucleophosmin (NPM), promyelocytic leukemia zinc finger (PLZF), nuclear mitotic apparatus (NUMA), and Stat5b, but the clinical characteristics of APL without PML-RAR have not been fully clarified. We describe a 64-year-old man with NPM-RAR-positive APL who was receiving hemodialysis therapy for chronic uremia. Complete remission was achieved with ATRA monotherapy and was maintained for 18 months with consolidation chemotherapy. These findings suggest that ATRA can be used to treat APL patients with NPM/RAR as well as APL with PML/RAR.

DOI： 10.1532/IJH97.07036

臍帯血移植(CBT)後の免疫抑制療法の至適化に向けた移植後リンパ球の免疫動態の解析

塚田信弘, 石毛真行, 小沼貴晶, 友成章, 大井淳, 高橋聡, 渡辺信和, 中内啓光, 増子正義, 古川達雄, 相澤義房, 東條有伸

臨床血液 48 ( 9 ) 890 - 890 2007年9月

Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients 査読

Hidenobu Takahashi, Tatsuo Furukawa, Toshio Yano, Naoko Sato, Jun Takizawa, Tori Kurasaki, Takashi Abe, Miwako Narita, Masayoshi Masuko, Satoru Koyama, Ken Toba, Masuhiro Takahashi, Yoshifusa Aizawa

EXPERIMENTAL HEMATOLOGY 35 ( 7 ) 1091 - 1099 2007年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCIENCE INC

Objective. To identify leukemia-associated antigens, we applied the serological identification of antigens by the recombinant expression cloning (SEREX) method to a chronic myelogenous leukemia (CML) patient who achieved a cytogenetic response to interferon-alpha.
Materials and Methods. Immunoscreening of the cDNA library was performed with sera from a CML patient. Two isolated antigens were used to evaluate the expression pattern using Northern blot analysis and quantitative reverse transcriptase polymerase chain reaction. Western blotting and enzyme-linked immunosorbent assay were also performed for serological analysis.
Results. We identified 14 positive clones, representing five different antigens. Of these, two genes were further validated. One (clone 70) was the human polyribonucleotide nucleotidyltransferase 1 (PNPT1), which is the type I interferon (alpha/beta-responsive gene). The mRNA of clone 70 was ubiquitously expressed in normal human tissues. The other gene (clone 57) was the heat shock 70-kDa protein 4-like (HSPA4L), which is a member of the heat shock protein 110 family, whose mRNA is strongly expressed in normal human testis and overexpressed in leukemia cells. Seroactivity against HSPA4L was detected in 6 of 9 acute myeloid leukemia patients, 4 of 10 acute lymphoblastic leukemia patients, 9 of 11 CML patients, and none of 10 healthy volunteers. Leukemia patients had higher titer of the antibodies against the protein than healthy volunteers.
Conclusions. These results suggest that HSPA4L, a member of heat shock protein, is highly expressed by leukemia cells, and elicit humoral immune responses in leukemia patients, and it might be a potential target for antileukemia therapy and an antigen-specific immunotherapy for leukemia.

DOI： 10.1016/j.exphem.2007.03.015

Plasma brain natriuretic peptide during myeloablative stem cell transplantation. 査読

Masuko M, Ito M, Kurasaki T, Yano T, Takizawa J, Toba K, Aoki S, Fuse I, Kodama M, Furukawa T, Aizawa Y

Internal medicine (Tokyo, Japan) 46 ( 9 ) 551 - 555 2007年

担当区分：筆頭著者,　責任著者記述言語：英語出版者・発行元：The Japanese Society of Internal Medicine

<b>Objective:</b> Cardiovascular complication is one of the serious complications in stem cell transplantation (SCT). We measured plasma brain natriuretic peptide (BNP) concentrations in patients who received SCT to evaluate possible cardiac toxicity of the regimens employed in SCT.<br> <b>Patients:</b> Ten patients with allogeneic SCT and 5 patients with autologous SCT using myeloablative conditioning regimens were enrolled. The preparative chemotherapy for 8 patients with allogeneic SCT included cyclophosphamide (60 mg/kg i.v. for 2 days) and other drugs and that for autologous SCT included cyclophosphamide (50 mg/kg for 2 days) and other drugs. Total body irradiation (TBI) was employed only in the patients who received allogeneic SCT.<br> <b>Method:</b> Plasma BNP was measured using a radioimmunoassay for human BNP before and after SCT.<br> <b>Results:</b> In 13 of 15 patients, BNP levels were elevated after SCT. In patients who received a total body irradiation (TBI) of 13.2 Gy, BNP levels were higher than those without irradiation (p=0.01). The BNP level reached a peak within 6 months after SCT in most patients and fell thereafter. But 7 of the 15 patients (46.7%) had an abnormally high level of plasma BNP even after 6 months of SCT which suggests subclinical myocardial damage.<br> <b>Conclusion:</b> A rise in plasma BNP was frequently observed after SCT, and may be considered to represent cardiac damage caused by the preparative chemotherapy and/or total body irradiation. Since a rise was noted 6 months after SCT, long-term evaluation of cardiac function is important.<br>

DOI： 10.2169/internalmedicine.46.6188

その他リンク： http://search.jamas.or.jp/link/ui/2007315596

Persistence of various chromosomal aberrations in recipient cells during complete remission after bone marrow transplantation followed by graft rejection 査読

M Masuko, T Furukawa, O Yersser, M Narita, K Toba, T Koike, Y Aizawa

LEUKEMIA RESEARCH 29 ( 9 ) 1083 - 1087 2005年9月

担当区分：筆頭著者,　責任著者記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

A 16-year-old boy in a second remission of acute lymphoblastic leukemia (ALL) had undergone transplantation of bone marrow from an unrelated donor. The conditioning regimen consisted of high-dose cytarabine, etoposide and 12 Gy of total-body irradiation. Although the donor marrow was rejected, hematopoiesis by the recipient himself recovered and he has remained in complete remission for more than 8 years after stem tell transplantation (SCT). Bone marrow karyotype analysis I month after SCT showed random chromosomal aberrations. Although complete remission was maintained, various chromosomal aberrations were detected in marrow cells, and in peripheral blood cells under phytohemagglutinin stimulation over 8 years. Moreover, a clone including del(20)(q11) appeared in marrow cells 7 months after SCT and thereafter was also detected 5 years later in the peripheral blood. This persistence of various chromosomal aberrations and a stable clone without evolution to myelodysplastic syndrome or leukemia support the multi step theory of leukemogenesis. (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.leukres.2005.01.018

High-dose cytosine arabinoside and etoposide with total body irradiation as a preparatory regimen for allogeneic hematopoietic stem-cell transplantation in patients with acute lymphoblastic leukemia 査読

N. Sato, Tatsouf Furukawa, T. Kuroha, S. Hashimoto, M. Masuko, H. Takahashi, T. Yano, T. Abe, I. Fuse, T. Koike, K. Kishi, Y. Aizawa

Bone Marrow Transplantation 34 ( 4 ) 299 - 303 2004年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

One approach to improving the outcome of allogeneic hematopoietic stem-cell transplantation for acute lymphoblastic leukemia (ALL) is to intensify the pretransplant conditioning regimen without increasing toxicity. We used an intensified conditioning regimen consisting of high-dose cytosine arabinoside (3 g/m2 twice daily i.v. for 3 consecutive days, total six doses), high-dose etoposide (1 g/m2 once daily i.v. during the first 2 days) and total body irradiation (TBI) (HDACE-TBI) in ALL patients. We retrospectively analyzed 21 patients treated with HDACE-TBI, of whom 18 were in complete remission (CR) and three were in non-CR at transplantation. Although gastrointestinal toxicities were common, critical regimen-related toxicities were not seen in any patients. One patient demonstrated veno-occlusive disease, which could be controlled conservatively. The disease-free survival rate of 18 patients in CR at transplantation was 61%. These results demonstrate that the HDACE-TBI combination regimen is a feasible alternative to other preparatory regimens and does not increase the regimen-related toxicity. © 2004 Nature Publishing Group All rights reserved.

DOI： 10.1038/sj.bmt.1704575

Acute promyelocytic leukemia developing in untreated essential thrombocythemia 査読

Naoaki Sato, Tatsuo Furukawa, Masayoshi Masuko, Shigeo Hashimoto, Hidenobu Takahashi, Miyako Baba, Koichi Inano, Noriatsu Suzuki, Ken Toba, Ichiro Fuse, Yoshifusa Aizawa

American Journal of Hematology 71 ( 2 ) 114 - 116 2002年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

We describe a patient with untreated essential thrombocythemia (ET) who developed microgranular variant of acute promyelocytic leukemia, 9 years after the initial diagnosis of ET. He achieved complete remission (CR) but relapsed 11 months later. After achieving the second CR, he received peripheral stem cell transplantation from his HLA complete-matched sibling. Five months after the transplantation, he relapsed again with meningeal infiltration of leukemic cells. In this paper, we review cases of promyelocytic transformation of myeloproliferative diseases (MPD) other than chronic myeloid leukemia (CML). To our knowledge, this is the first case of promyelocytic transformation of Philadelphia chromosome negative untreated ET, in whom both t(15
17) and PML-RARα fusion were proven. © 2002 Wiley-Liss, Inc.

DOI： 10.1002/ajh.10195

JAK2, complemented by a second signal from c-kit or flt-3, triggers extensive self-renewal of primary multipotential hemopoietic cells 査読

SM Zhao, K Zoller, M Masuko, P Rojnuckarin, XXO Yang, E Parganas, K Kaushansky, JN Ihle, T Papayannopoulou, DM Willerford, T Clackson, CA Blau

EMBO JOURNAL 21 ( 9 ) 2159 - 2167 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NATURE PUBLISHING GROUP

Defining signals that can support the self-renewal of multipotential hemopoietic progenitor cells (MHPCs) is pertinent to understanding leukemogenesis and may be relevant to developing stem cell-based therapies. Here we define a set of signals, JAK2 plus either c-kit or flt-3, which together can support extensive MHPC self-renewal. Phenotypically and functionally distinct populations of MHPCs were obtained, depending on which receptor tyrosine kinase, c-kit or flt-3, was activated. Self-renewal was abrogated in the absence of STAT5a/b, and in the presence of inhibitors targeting either the mitogen-activated protein kinase or phosphatidylinositol 3' kinase pathways. These findings suggest that a simple two-component signal can drive MHPC self-renewal.

DOI： 10.1093/emboj/21.9.2159

Receptor specificity in the self-renewal and differentiation of primary multipotential hemopoietic cells 査読

H Zeng, M Masuko, LQ Jin, T Neff, KG Otto, CA Blau

BLOOD 98 ( 2 ) 328 - 334 2001年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：AMER SOC HEMATOLOGY

To determine whether cytokine-induced signals generate unique responses in multipotential hemopoietic progenitor cells, the signaling domains of 3 different growth factor receptors (MpI, granulocyte-colony-stimulating factor [G-CSF] receptor, and Flt-3) were inserted into mouse primary bone marrow cells. To circumvent the activation of endogenous receptors, each signaling domain was incorporated into an FK506 binding protein (FKBP) fusion to allow for its specific activation using synthetic FKBP ligands, Each signaling domain supported the growth of Ba/F3 cells; however, only MpI supported the sustained growth of transduced marrow cells, with a dramatic expansion of multipotential progenitors and megakaryocytes. These findings demonstrate that the self-renewal and differentiation of multipotential progenitor cells can be influenced through distinct, receptor-initiated signaling pathways. (C) 2001 by The American Society of Hematology.

DOI： 10.1182/blood.V98.2.328

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