Noriko Doki
University of Tokyo
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Featured researches published by Noriko Doki.
Blood | 2015
Yasuo Morishima; Koichi Kashiwase; Keitaro Matsuo; Fumihiro Azuma; Satoko Morishima; Makoto Onizuka; Toshio Yabe; Makoto Murata; Noriko Doki; Tetsuya Eto; Takehiko Mori; Koichi Miyamura; Hiroshi Sao; Tatsuo Ichinohe; Hiroo Saji; Shunichi Kato; Yoshiko Atsuta; Keisei Kawa; Yoshihisa Kodera; Takehiko Sasazuki
We hypothesized that the compatibility of each HLA loci between donor and patient induced divergent transplant-related immunologic responses, which attributed to the individualized manifestation of clinical outcomes. Here, we analyzed 7898 Japanese pairs transplanted with T-cell-replete marrow from an unrelated donor with complete HLA allele typing data. Multivariable competing risk regression analyses were conducted to evaluate the relative risk (RR) of clinical outcomes after transplantation. A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD. Of note, only HLA-C and HLA-DPB1 mismatch reduced leukemia relapse, and this graft-versus-leukemia effect of HLA-DPB1 was independent of chronic GVHD. HLA-DRB1 and HLA-DQB1 double (DRB1_DQB1) mismatch was revealed to be a significant RR for acute GVHD and mortality, whereas single mismatch was not. Thus, the number of HLA-A, -B, -C, -DPB1, and DRB1_DQB1 mismatches showed a clear-cut risk difference for acute GVHD, whereas the number of mismatches for HLA-A, -B, -C, and DRB1_DQB1 showed the same for mortality. In conclusion, we determined the biological response to HLA locus mismatch in transplant-related immunologic events, and provide a rationale for use of a personalized algorithm for unrelated donor selection.
Blood | 2016
Kazuhiko Kakihana; Yuki Fujioka; Wataru Suda; Yuho Najima; Go Kuwata; Satoshi Sasajima; Iyo Mimura; Hidetoshi Morita; Daisuke Sugiyama; Hiroyoshi Nishikawa; Masahira Hattori; Yutaro Hino; Shuntaro Ikegawa; Keita Yamamoto; Takashi Toya; Noriko Doki; Koichi Koizumi; Kenya Honda; Kazuteru Ohashi
Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.
Blood | 2011
Naoko Kato; Jiro Kitaura; Noriko Doki; Yukiko Komeno; Naoko Watanabe-Okochi; Katsuhiro Togami; Fumio Nakahara; Toshihiko Oki; Yutaka Enomoto; Yumi Fukuchi; Hideaki Nakajima; Yuka Harada; Hironori Harada; Toshio Kitamura
Two types of mutations of a transcription factor CCAAT-enhancer binding protein α (C/EBPα) are found in leukemic cells of 5%-14% of acute myeloid leukemia (AML) patients: N-terminal mutations expressing dominant negative p30 and C-terminal mutations in the basic leucine zipper domain. Our results showed that a mutation of C/EBPα in one allele was observed in AML after myelodysplastic syndrome, while the 2 alleles are mutated in de novo AML. Unlike an N-terminal frame-shift mutant (C/EBPα-N(m))-transduced cells, a C-terminal mutant (C/EBPα-C(m))-transduced cells alone induced AML with leukopenia in mice 4-12 months after bone marrow transplantation. Coexpression of both mutants induced AML with marked leukocytosis with shorter latencies. Interestingly, C/EBPα-C(m) collaborated with an Flt3-activating mutant Flt3-ITD in inducing AML. Moreover, C/EBPα-C(m) strongly blocked myeloid differentiation of 32Dcl3 cells, suggesting its class II mutation-like role in leukemogenesis. Although C/EBPα-C(m) failed to inhibit transcriptional activity of wild-type C/EBPα, it suppressed the synergistic effect between C/EBPα and PU.1. On the other hand, C/EBPα-N(m) inhibited C/EBPα activation in the absence of PU.1, despite low expression levels of p30 protein generated by C/EBPα-N(m). Thus, 2 types of C/EBPα mutations are implicated in leukemo-genesis, involving different and cooperating molecular mechanisms.
International Journal of Hematology | 2007
Hideki Uchiumi; Takafumi Matsushima; Arito Yamane; Noriko Doki; Hiroyuki Irisawa; Takayuki Saitoh; Tohru Sakura; Takahiro Jimbo; Hiroshi Handa; Norifumi Tsukamoto; Masamitsu Karasawa; Shuichi Miyawaki; Hirokazu Murakami; Yoshihisa Nojima
Disseminated intravascular coagulation (DIC) is one of the important complications to develop in patients with acute myeloid leukemia (AML). While acute promyelocytic leukemia (APL) is a strong risk factor for DIC, other clinical features have not been fully defined. We retrospectively analyzed 161 consecutive adult patients with de novo non-APL AML. DIC was diagnosed in 52 patients (32%); 28 patients at diagnosis and 24 soon after the initiation of induction chemotherapy. Leukocyte counts, C-reactive protein, and lactate dehydrogenase were significantly higher in the DIC+ group. Negative expressions of CD13, CD19, CD34, and HLA-DR were more prevalent in the DIC+ group. On multivariate logistic-regression analysis, variables that were independently associated with the development of DIC were high C-reactive protein, high leukocyte count, negative expressions of CD13 and HLA-DR, and cytogenetics with a normal karyotype or 11q23 abnormality. Although DIC is considered to be associated with serious morbidity and occasional mortality, we did not find any significant differences in the complete remission rate, overall or disease-free survival between DIC+ and DIC- groups. This study is the first to define the clinical characteristics associated with DIC in patients with non-APL AML, but exactly how and when DIC should be treated remains to be determined.
Blood | 2013
Yuka Harada; Daichi Inoue; Ye Ding; Jun Imagawa; Noriko Doki; Hirotaka Matsui; Takashi Yahata; Hiromichi Matsushita; Kiyoshi Ando; Goro Sashida; Atsushi Iwama; Toshio Kitamura; Hironori Harada
RUNX1/AML1 mutations have been identified in myelodysplastic syndromes (MDSs). In a mouse bone marrow transplantation model, a RUNX1 mutant, D171N, was shown to collaborate with Evi1 in the development of MDSs; however, this is rare in humans. Using enforced expression in human CD34(+) cells, we showed that the D171N mutant, the most frequent target of mutation in the RUNX1 gene, had an increased self-renewal capacity, blocked differentiation, dysplasia in all 3 lineages, and tendency for immaturity, but no proliferation ability. BMI1 overexpression was observed in CD34(+) cells from the majority of MDS patients with RUNX1 mutations, but not in D171N-transduced human CD34(+) cells. Cotransduction of D171N and BMI1 demonstrated that BMI1 overexpression conferred proliferation ability to D171N-transduced cells in both human CD34(+) cells and a mouse bone marrow transplantation model. Stepwise transduction of D171N followed by BMI1 in human CD34(+) cells resulted in long-term proliferation with a retained CD34(+) cell fraction, which is quite similar to the phenotype in patients with higher-risk MDSs. Our results indicate that BMI1 overexpression is one of the second hit partner genes of RUNX1 mutations that contribute to the development of MDSs.
Clinical Chemistry | 2014
Jun Aoki; Kazuteru Ohashi; Masato Mitsuhashi; Taku Murakami; Melanie Oakes; Takeshi Kobayashi; Noriko Doki; Kazuhiko Kakihana; Hisashi Sakamaki
BACKGROUND Bone marrow (BM) aspiration often can be a painful medical procedure. It is unavoidable, however, because hematopoietic precursor cells (HPC) exist only in BM and few escape to peripheral blood (PB). We hypothesized that HPCs might release exosomes and microvesicles (EMV) in BM, and the resulting EMV would penetrate into PB. Such BM-derived EMV might be identified in PB by measuring specific mRNAs produced by HPC. METHODS Human plasma was applied to an EMV-capture filter plate. After centrifugation, captured EMV were lysed on the filter plate. Resulting lysates were transferred to an oligo(dT)-immobilized microplate for mRNA isolation followed by reverse transcription PCR (RT-PCR). Using this system, myeloid-, erythroid-, and megakaryocyte-lineage-specific poly(A)(+) mRNAs were quantified in plasma obtained from 18 patients who had undergone hematopoietic stem cell transplantation (HSCT). RESULTS When fluorescent liposomes were applied to the filter plate, more than 95% of applied liposomes were absorbed. When human plasma was applied, a scanning electron microscope showed EMV-like particles on the membrane of the filter plate. After RT-PCR, various HPC-specific mRNAs were detected, and the results were equivalent to those derived from the standard ultracentrifugation method. The levels of these mRNAs were undetectable after HSCT and became detectable 1-2 weeks after HSCT, a substantially earlier time point than with traditional hematological analysis. The recovery of EMV mRNA at day 15 corresponded to the final clinical outcome at day 180. CONCLUSIONS HPC-derived mRNAs in plasma EMV may represent new biomarkers for the assessment of BM condition and could reduce the necessity for frequent BM aspiration.
European Journal of Haematology | 2015
Hiroaki Shimizu; Takayuki Saitoh; Shinichiro Machida; Shinichi Kako; Noriko Doki; Takehiko Mori; Toru Sakura; Yoshinobu Kanda; Heiwa Kanamori; Shuichi Miyawaki; Shinichiro Okamoto
Adult patients with mixed phenotype acute leukemia (MPAL) have a poor prognosis, and the therapeutic role of allogeneic stem cell transplantation (allo‐SCT) for MPAL remains to be elucidated. Thus, we retrospectively assessed the efficacy of allo‐SCT for MPAL. Eighteen patients with MPAL were identified from the transplant outcome database of Kanto Study Group for Cell Therapy (KSGCT). We also selected 215 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) as control cohorts using an optimal matching method. The 5‐yr overall survival (OS) rate of patients with MPAL was 48.1%, and patients in remission at the time of transplant showed significantly better survival than those not in remission (5‐yr OS: 71.8% vs. 0%, P = 0.001). No significant differences were seen in OS when stratifying patients according to immunophenotype, cytogenetic abnormalities, or the type of induction therapy. The 5‐yr OS rate of patients with MPAL was not significantly different compared with AML control patients (48.1% vs. 48.1%; P = 0.855) or ALL control patients (48.1% vs. 37.8%; P = 0.426). These results suggested that allo‐SCT is an effective treatment for MPAL, especially early in the disease course, and innovative transplant approaches are warranted to improve the transplant outcome of patients with MPAL who are not in remission.
Transplant Infectious Disease | 2013
Noriko Doki; S. Miyawaki; Masatsugu Tanaka; D. Kudo; A. Wake; Kumi Oshima; H. Fujita; T. Uehara; R. Hyo; Taisuke Mori; Satoshi Takahashi; Shinichiro Okamoto; Hisashi Sakamaki
Varicella zoster virus (VZV) disease is one of the major infectious complications that can occur after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Many reports have shown visceral VZV infection, a special type of VZV disease, to be rare. However, few studies so far have included a large number of patients.
British Journal of Haematology | 2015
Gaku Oshikawa; Kazuhiko Kakihana; Makoto Saito; Jun Aoki; Yuho Najima; Takeshi Kobayashi; Noriko Doki; Hisashi Sakamaki; Kazuteru Ohashi
166, 702–710. Moreau, P., Pylypenko, H., Grosicki, S., Karamanesht, I., Leleu, X., Grishunina, M., Rekhtman, G., Masliak, Z., Robak, T., Shubina, A., Arnulf, B., Kropff, M., Cavet, J., Esseltine, D.L., Feng, H., Girgis, S., van de Velde, H., Deraedt, W. & Harousseau, J.L. (2011) Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, noninferiority study. The Lancet Oncology, 12, 431–440. Reeder, C.B., Reece, D.E., Kukreti, V., Chen, C., Trudel, S., Hentz, J., Noble, B., Pirooz, N.A., Spong, J.E., Piza, J.G., Zepeda, V.H., Mikhael, J.R., Leis, J.F., Bergsagel, P.L., Fonseca, R. & Stewart, A.K. (2009) Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia, 23, 1337–1341. Reeder, C.B., Reece, D.E., Kukreti, V., Mikhael, J.R., Chen, C., Trudel, S., Laumann, K., Vohra, H., Fonseca, R., Bergsagel, P.L., Leis, J.F., Tiedemann, R. & Stewart, A.K. (2014) Long-term survival with cyclophosphamide, bortezomib and dexamethasone induction therapy in patients with newly diagnosed multiple myeloma. British Journal of Haematology, 167, 6563–6564. Richardson, P.G., Weller, E., Lonial, S., Jakubowiak, A.J., Jagannath, S., Raje, N.S., Avigan, D.E., Xie, W., Ghobrial, I.M., Schlossman, R.L., Mazumder, A., Munshi, N.C., Vesole, D.H., Joyce, R., Kaufman, J.L., Doss, D., Warren, D.L., Lunde, L.E., Kaster, S., Delaney, C., Hideshima, T., Mitsiades, C.S., Knight, R., Esseltine, D.L. & Anderson, K.C. (2010) Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood, 116, 679–686.
Transplant Infectious Disease | 2014
Y. Umezawa; Kazuhiko Kakihana; G. Oshikawa; Takeshi Kobayashi; Noriko Doki; Hisashi Sakamaki; Kazuteru Ohashi
We retrospectively analyzed 80 instances of varicella zoster virus (VZV) disease in 72 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) and examined the clinical differences between localized and disseminated disease. Risk factors for developing VZV dissemination were also evaluated.