Mineo Kurokawa

Publications of Mineo Kurokawa

• Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples.

  Authors: Keiki Kumano, Shunya Arai, Masataka Hosoi, Kazuki Taoka, Naoya Takayama, Makoto Otsu, Genta Nagae, Koki Ueda, Kumi Nakazaki, Yasuhiko Kamikubo, Koji Eto, Hiroyuki Aburatani, Hiromitsu Nakauchi, Mineo Kurokawa

  Blood. 05/2012;

  Induced pluripotent stem cells (iPSCs) can be generated by the expression of defined transcription factors not only from normal tissue, but also from malignant cells. Cancer-derived iPSCs areInduced pluripotent stem cells (iPSCs) can be generated by the expression of defined transcription factors not only from normal tissue, but also from malignant cells. Cancer-derived iPSCs are expected to provide a novel experimental opportunity to establish the disease model. We generated iPSCs from imatinib-sensitive chronic myelogenous leukemia (CML) patient samples. Remarkably, the CML-iPSCs were resistant to imatinib although they consistently expressed BCR-ABL oncoprotein. In CML-iPSCs, the phosphorylation of ERK1/2, AKT, and JNK, which are essential for the maintenance of both BCR-ABL (+) leukemia cells and iPSCs, were unchanged after imatinib treatment, whereas the phosphorylation of STAT5 and CRKL was significantly decreased. These results suggest that the signaling for iPSCs maintenance compensates for the inhibition of BCR-ABL. CML-iPSC-derived hematopoietic cells recovered the sensitivity to imatinib although CD34(+)38(-)90(+)45(+) immature cells were resistant to imatinib, which recapitulated the pathophysiological feature of the initial CML. CML-iPSCs provide us with a novel platform to investigate CML pathogenesis on the basis of patient-derived samples.

• Intensive chemotherapy for elderly patients with acute myelogeneous leukemia: a propensity score analysis by the Japan Hematology and Oncology Clinical Study Group (J-HOCS).

  Authors: Kumi Oshima, Wataru Takahashi, Yuki Asano-Mori, Koji Izutsu, Tsuyoshi Takahashi, Yukihiro Arai, Yasunori Nakagawa, Kensuke Usuki, Mineo Kurokawa, Kenshi Suzuki, Kinuko Mitani, Yoshinobu Kanda

  Annals of hematology. 05/2012;

  The prognosis of acute myelogenous leukemia (AML) in the elderly patients is extremely poor. Although several previous studies have suggested that intensive chemotherapy is associated with a betterThe prognosis of acute myelogenous leukemia (AML) in the elderly patients is extremely poor. Although several previous studies have suggested that intensive chemotherapy is associated with a better prognosis, there may have been a selection bias. Therefore, we retrospectively evaluated the impact of intensive chemotherapy for AML in the elderly by stratifying patients according to a propensity score. Eighty-one AML patients aged 70 years or more were included in this study. Patients with acute promyelocytic leukemia were not included. A propensity score for the use of intensive chemotherapy was calculated from four factors at diagnosis. Forty-five patients received intensive chemotherapy, whereas 36 received low-dose or no chemotherapy. We stratified the patients into quartiles based on the propensity score. The numbers of patients in the first, second, third, and forth quartiles who received intensive chemotherapy were 5 of 21, 10 of 20, 12 of 20, and 18 of 20, respectively. A stratified log-rank test showed significantly better overall survival in the intensive chemotherapy group (P = 0.0088). Especially, in the combined second and third quartiles, which showed an equal tendency for intensive and non-intensive strategies; overall survival at 3 years was 37.5 % for the intensive chemotherapy group and 13.0 % for the non-intensive chemotherapy group (P = 0.0022). A conventional multivariate analysis confirmed that intensive chemotherapy was beneficial (hazard ratio 0.50, 95 % confidence interval 0.27-0.93, P = 0.028). In conclusion, intensive chemotherapy may prolong overall survival in elderly AML patients who are considered to be able to tolerate such treatment based on factors at diagnosis.

• Thalidomide maintenance therapy for patients with multiple myeloma: Meta-analysis.

  Authors: Yuki Kagoya, Yasuhito Nannya, Mineo Kurokawa

  Leukemia research. 05/2012;

  We performed a meta-analysis of randomized controlled trials comparing thalidomide maintenance with other regimens after induction chemotherapy for multiple myeloma. Overall, 6 trials including 2786We performed a meta-analysis of randomized controlled trials comparing thalidomide maintenance with other regimens after induction chemotherapy for multiple myeloma. Overall, 6 trials including 2786 patients were identified. Patients treated with thalidomide maintenance had marginally better overall survival (hazard ratio HR 0.83, P=0.07). The improvement was especially prominent in a subgroup of studies using corticosteroids with thalidomide (HR 0.70, P=0.02). Thalidomide improved progression-free survival (HR 0.65, P<0.01), but had more frequent venous thrombosis (risk difference 0.024, P<0.05) and peripheral neuropathy (risk difference 0.072, P<0.01). These results suggest that thalidomide maintenance with corticosteroids is effective in prolonging survival for multiple myeloma.

• Evaluation of procalcitonin with liquid-phase binding assay in hematological malignancy.

  Authors: Junji Koya, Yasuhito Nannya, Mineo Kurokawa

  Clinica chimica acta; international journal of clinical chemistry. 05/2012;

  BACKGROUND: To determine procalcitonin (PCT) levels in blood, a newly analyzer based on liquid-phase binding assay (LBA) was developed (micro-total analysis system, μTAS). We evaluated analytical andBACKGROUND: To determine procalcitonin (PCT) levels in blood, a newly analyzer based on liquid-phase binding assay (LBA) was developed (micro-total analysis system, μTAS). We evaluated analytical and clinical performance of this system in comparison with autoanalyzer based on chemiluminescence enzyme immunoassay (CLEIA), which is widely-used but takes much longer time than LBA. METHODS: A total of 518 serum samples from 28 patients undergoing hematopoietic stem cell transplantation were analyzed. The correlation between the 2 methods and the comparison of the each area under the receiver operating characteristics curve (AUC) for distinguishing bacterial or fungal infections from other events were evaluated. RESULTS: The minimum detection limit of serum PCT levels by LBA was 0.02ng/ml. There was an excellent correlation between the two methods in all samples (r(2)=0.99), the samples obtained on days of fever onset (r(2)=0.99), and the samples collected in neutropenic state (r(2)=0.99). The AUC for detection of bacterial or fungal infection on the onset of fever was not significantly different between LBA and CLEIA (0.80 by LBA and 0.82 by CLEIA, P=0.19). CONCLUSIONS: The PCT measurement using LBA was well correlated with conventional method based on CLEIA and had enough clinical performance to detect bacterial or fungal infection in clinical setting.

• Usefulness of double-balloon enteroscopy for evaluation of duodenal follicular lymphoma.

  Authors: Sho Hangai, Fumihiko Nakamura, Atsuo Yamada, Hirotsugu Watabe, Motoshi Ichikawa, Kazuhiko Koike, Mineo Kurokawa

  Annals of hematology. 04/2012;

• An open-label extension study evaluating the safety and efficacy of romiplostim for up to 3.5 years in thrombocytopenic Japanese patients with immune thrombocytopenic purpura (ITP).

  Authors: Yukari Shirasugi, Kiyoshi Ando, Koji Miyazaki, Yoshiaki Tomiyama, Koji Iwato, Shinichiro Okamoto, Mineo Kurokawa, Keita Kirito, Satoshi Hashino, Haruhiko Ninomiya, Shinichiro Mori, Yuji Yonemura, Kensuke Usuki, Helen Wei, Richard Lizambri

  International journal of hematology. 04/2012;

  Long-term use of the thrombopoietin mimetic romiplostim was examined in Japanese patients with chronic immune thrombocytopenic purpura (ITP) in this open-label extension. The starting dose ofLong-term use of the thrombopoietin mimetic romiplostim was examined in Japanese patients with chronic immune thrombocytopenic purpura (ITP) in this open-label extension. The starting dose of romiplostim was the previous trial dose or 3 μg/kg/week, which was titrated up to 10 μg/kg/week to maintain platelet counts between 50 and 200 × 10(9)/L. As of April 2010, 44 patients had enrolled; 71 % women, median age 55.5 years, with five patients discontinuing romiplostim due to patient request (2), administrative decision (2), or not achieving study-defined platelet response (1). Median treatment duration was 100 weeks; median average weekly dose was 3.8 μg/kg. Twenty-eight patients (64 %) self-injected romiplostim. The most frequent adverse events were nasopharyngitis and headache. Nine patients (20 %) had a total of 14 serious adverse events (0.31/100 patient-weeks); of these, only oral hemorrhage was considered treatment related. Fifty hemorrhagic adverse events were reported in 20 patients (46 %) (1.12/100 patient-weeks). Ninety-six percent of patients had a platelet response (doubling of baseline platelet count and platelet count ≥50 × 10(9)/L). Of the 25 patients receiving concurrent ITP therapy at baseline, all reduced or discontinued the therapy. Eight patients (18 %) received rescue medications. Administration of up to 3.5 years of romiplostim increased platelet counts and was well tolerated in Japanese patients with chronic ITP.

• Pituitary lymphoma developing within pituitary adenoma.

  Authors: Ken Morita, Fumihiko Nakamura, Yasuhiko Kamikubo, Naoaki Mizuno, Masashi Miyauchi, Go Yamamoto, Yasuhito Nannya, Motoshi Ichikawa, Mineo Kurokawa

  International journal of hematology. 04/2012;

  Lymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with aLymphoma occurring in the pituitary gland is an exceedingly infrequent event. Here, we describe a case of pituitary lymphoma complicating recurrent pituitary adenoma. A 56-year-old male with a history of pituitary adenoma was diagnosed with diffuse large B-cell lymphoma (DLBCL) of the left ocular adnexa, which was successfully treated by standard chemotherapy and local radiotherapy. Eight months later, he complained of diplopia and bitemporal hemianopia. Brain magnetic resonance imaging detected a suprasellar tumor. Transsphenoidal biopsy of the mass was performed, and histopathological examination revealed DLBCL admixed with pituitary adenoma. On a review of the literature, we found that pituitary lymphoma developing within adenoma is a recurrent phenomenon. The composite tumor is likely to be characterized by suprasellar involvement and presentation of visual disturbances. Moreover, in the present case, the suprasellar tumor remained visible after autologous peripheral stem cell transplant, likely due to the residual pituitary adenoma. We therefore recommend that refractory pituitary lymphoma should be vigorously biopsied in search of possibly underlying adenoma.

• EVI1, stem cell self-renewal and leukemogenesis.

  Authors: Keisuke Kataoka, Mineo Kurokawa

  Cancer science. 04/2012;

  It has become evident that acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs). Recent gene expressionIt has become evident that acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSCs). Recent gene expression profile analysis of human LSC and hematopoietic stem cell (HSC) populations identified a key transcriptional program shared by LSCs and HSCs, which is associated with adverse outcomes in AML patients. One molecule that has been established as a pivotal regulator in fine-tuning of stem cell properties as well as a potent oncogenic determinant is Ecotropic viral integration site 1 (EVI1). EVI1 is a transcription factor that has stem cell-specific expression pattern and is essential for the regulation of HSC self-renewal. This gene is notorious for its involvement in AML, as its activation confers extremely poor prognosis in patients with AML. Molecular analysis has identified a variety of gene products that are involved in HSC regulation as downstream targets or interacting proteins of EVI1. Thus, exploration of the molecular pathogenesis underlying EVI1-related leukemogenesis provides insights into how shared stemness transcriptional programs contribute to leukemia progression and therapeutic resistance in AML. Here we will review the current knowledge regarding the role of EVI1 in HSC self-renewal and leukemogenesis and highlight the relationship between stem cell self-renewal properties and adverse outcome in myeloid malignancies.

• Multiple phosphorylation sites are important for RUNX1 activity in early hematopoiesis and T-cell differentiation.

  Authors: Mayumi Yoshimi, Susumu Goyama, Masahito Kawazu, Masahiro Nakagawa, Motoshi Ichikawa, Yoichi Imai, Keiki Kumano, Takashi Asai, James C Mulloy, Andrew S Kraft, Tsuyoshi Takahashi, Naoki Shirafuji, Mineo Kurokawa

  European journal of immunology. 04/2012; 42(4):1044-50.

  RUNX1 is essential for definitive hematopoiesis and T-cell differentiation. It has been shown that RUNX1 is phosphorylated at specific serine and threonine residues by several kinase families.RUNX1 is essential for definitive hematopoiesis and T-cell differentiation. It has been shown that RUNX1 is phosphorylated at specific serine and threonine residues by several kinase families. However, it remains unclear whether RUNX1 phosphorylation is absolutely required for its biological functions. Here, we evaluated hematopoietic activities of RUNX1 mutants with serine (S)/threonine (T) to alanine (A), aspartic acid (D), or glutamic acid (E) mutations at phosphorylation sites using primary culture systems. Consistent with the results of knockin mice, RUNX1-2A, carrying two phospho-deficient mutations at S276 and S293, retained hematopoietic activity. RUNX1-4A, carrying four mutations at S276, S293, T300, and S303, showed impaired T-cell differentiation activity, but retained the ability to rescue the defective early hematopoiesis of Runx1-deficient cells. Notably, RUNX1-5A, carrying five mutations at S276, S293, T300, S303, and S462, completely lost its hematopoietic activity. In contrast, the phospho-mimic proteins RUNX1-4D/E and RUNX1-5D/E exhibited normal function. Our study identifies multiple phosphorylation sites that are indispensable for RUNX1 activity in hematopoiesis.

• Related transplantation with HLA-1 Ag mismatch in the GVH direction and HLA-8/8 allele-matched unrelated transplantation: a nationwide retrospective study.

  Authors: Junya Kanda, Hiroh Saji, Takahiro Fukuda, Takeshi Kobayashi, Koichi Miyamura, Tetsuya Eto, Mineo Kurokawa, Heiwa Kanamori, Takehiko Mori, Michihiro Hidaka, Koji Iwato, Takashi Yoshida, Hisashi Sakamaki, Junji Tanaka, Keisei Kawa, Yasuo Morishima, Ritsuro Suzuki, Yoshiko Atsuta, Yoshinobu Kanda

  Blood. 03/2012; 119(10):2409-16.

  To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A,To clarify which is preferable, a related donor with an HLA-1 Ag mismatch at the HLA-A, HLA-B, or HLA-DR loci in the graft-versus-host (GVH) direction (RD/1AG-MM-GVH) or an HLA 8/8-allele (HLA-A, HLA-B, HLA-C, and HLA-DRB1)-matched unrelated donor (8/8-MUD), we evaluated 779 patients with acute leukemia, chronic myelogenous leukemia, or myelodysplastic syndrome who received a T cell-replete graft from an RD/1AG-MM-GVH or 8/8-MUD. The use of an RD/1AG-MM-GVH donor was significantly associated with a higher overall mortality rate than the use of an 8/8-MUD in a multivariate analysis (hazard ratio, 1.49; P < .001), and this impact was statistically significant only in patients with standard-risk diseases (P = .001). Among patients with standard-risk diseases who received transplantation from an RD/1AG-MM-GVH donor, the presence of an HLA-B Ag mismatch was significantly associated with a lower overall survival rate than an HLA-DR Ag mismatch because of an increased risk of treatment-related mortality. The HLA-C Ag mismatch or multiple allelic mismatches were frequently observed in the HLA-B Ag-mismatched group, and were possibly associated with the poor outcome. In conclusion, an 8/8-MUD should be prioritized over an RD/1AG-MM-GVH donor during donor selection. In particular, an HLA-B Ag mismatch in the GVH direction has an adverse effect on overall survival and treatment-related mortality in patients with standard-risk diseases.

• Hyperlipidemia after allogeneic stem cell transplantation: prevalence, risk factors, and impact on prognosis.

  Authors: Yuki Kagoya, Sachiko Seo, Yasuhito Nannya, Mineo Kurokawa

  Clinical transplantation. 03/2012; 26(2):E168-75.

  Hyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus-host disease (GVHD) or calcineurinHyperlipidemia is one of the late complications after allogeneic stem cell transplantation (SCT). Although intrahepatic cholestasis caused by chronic graft-versus-host disease (GVHD) or calcineurin inhibitors has been considered as possible etiologies, its prevalence, risk factors, and impact on prognosis have not been investigated well. We performed a retrospective analysis of 194 patients who underwent allogeneic SCT between 1995 and 2008 in our institute and survived more than 100 d after SCT. Overall, 83 (42.8%) and 99 (50.8%) patients developed hypercholesterolemia (≥240 mg/dL) and hypertriglyceridemia (≥200 mg/dL), respectively. In multivariate analysis, the development of chronic GVHD (hazard ratio [HR] 2.04, p < 0.05) and steroid use (HR 2.24, p < 0.01) were independently associated with hypercholesterolemia, while administration of calcineurin inhibitors was not. As for the prognostic impact, multivariate analysis showed that the patients with hypercholesterolemia had a tendency of lower rate of relapse (HR: 0.44, p = 0.07). There was no difference in non-relapse mortality or overall survival between the groups. In conclusion, the development of hypercholesterolemia is regarded as one of the symptoms accompanied with chronic GVHD and might indicate a better control of the primary disease.

• Hepatocellular carcinoma in cirrhotic liver with graft-versus-host disease.

  Authors: Akihide Yoshimi, Go Yamamoto, Tadashi Goto, Kazuhiko Koike, Mineo Kurokawa

  Annals of hematology. 02/2012;

• Primary MALT lymphoma of the urinary bladder in the background of interstitial cystitis.

  Authors: Ken Morita, Fumihiko Nakamura, Yasuhito Nannya, Akira Nomiya, Shunya Arai, Motoshi Ichikawa, Yukio Homma, Mineo Kurokawa

  Annals of hematology. 02/2012;

• Fludarabine may overcome resistance to rituximab in IgM-related neuropathy.

  Authors: Junji Koya, Atsushi Iwata, Fumihiko Nakamura, Yu Nagashima, Motoshi Ichikawa, Shoji Tsuji, Mineo Kurokawa

  Journal of the neurological sciences. 01/2012;

  Rituximab, a monoclonal antibody directed against CD20, became widely used for the treatment of immunoglobulin M (IgM)-related neuropathy. However, response rate by rituximab monotherapy is no moreRituximab, a monoclonal antibody directed against CD20, became widely used for the treatment of immunoglobulin M (IgM)-related neuropathy. However, response rate by rituximab monotherapy is no more than 30%. Previous studies revealed that fludarabine acts synergistically with rituximab in vitro and that fludarabine also ameliorates IgM-related neuropathy in a subset of patients. Here we present two cases of IgM-related neuropathy in the background of Waldenström macroglobulinaemia, including one with rituximab resistance. They showed marginal to high titres of both anti-myelin associated glycoprotein and anti-sulphate-3-glucuronyl paragloboside antibodies, and their symptoms were featured by prominent motor deterioration. The combination therapy with rituximab and fludarabine stabilised or improved neuropathic symptoms with tolerable adverse events. Fludarabine may have a potential to overcome rituximab resistance. In conclusion, combination therapy with rituximab and fludarabine should be considered for IgM-related neuropathy, especially when efficacy of rituximab monotherapy is insufficient.

• Comparison between Pulsed High-Dose Dexamethasone and Daily Corticosteroid Therapy for Adult Primary Immune Thrombocytopenia: A Retrospective Study.

  Authors: Kumi Nakazaki, Masataka Hosoi, Akira Hangaishi, Motoshi Ichikawa, Yasuhito Nannya, Mineo Kurokawa

  Internal medicine (Tokyo, Japan). 01/2012; 51(8):859-63.

  Objective Recently, pulsed high-dose dexamethasone (HD-Dexa) therapy was proposed as a possible alteration for the classical prednisolone (PSL) therapy for primary immune thrombocytopenia (ITP)Objective Recently, pulsed high-dose dexamethasone (HD-Dexa) therapy was proposed as a possible alteration for the classical prednisolone (PSL) therapy for primary immune thrombocytopenia (ITP) patients, however it remains to be confirmed which of these remedies is superior. So the objective of this study is to compare the efficacy and the sustainability of these options. Methods The first-line therapy at our institute for untreated adult ITP cases was accordingly changed as follows, and we retrospectively evaluated the outcomes: 1) daily administration of 0.5-1 mg/kg PSL for 2-4 weeks and subsequently stepwise reduction, 2) one course of HD-Dexa (40 mg/day for four consecutive days, 1xHD-Dexa), 3) three courses of the same dose of HD-Dexa (3xHD-Dexa) repeated biweekly. This study was approved by the ethical committee of the University of Tokyo. Results Twenty-five patients were enrolled consecutively. A good initial response was attained through all the regimens. Meanwhile, time to next treatment for lack of response or relapse was significantly longer in the PSL group than in the other groups (log-rank test, PSL vs. 1xHD-Dexa p<0.001, PSL vs. 3xHD-Dexa p=0.0053, respectively). Additionally, PSL regimen conferred a significantly longer duration time of response (PSL vs. 1xHD-Dexa p=0.0024, PSL vs. 3xHD-Dexa p=0.028, respectively) and CR (PSL vs. 1xHD-Dexa p=0.012, PSL vs. 3xHD-Dexa p=0.0090, respectively). No patient discontinued the treatment due to side effects in this study. Conclusion PSL regimen was considered to be superior to pulsed HD-Dexa regimens in the sustainability of response.

• The effect of iron overload and chelation on erythroid differentiation.

  Authors: Kazuki Taoka, Keiki Kumano, Fumihiko Nakamura, Masataka Hosoi, Susumu Goyama, Yoichi Imai, Akira Hangaishi, Mineo Kurokawa

  International journal of hematology. 12/2011; 95(2):149-59.

  We investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit(+) progenitor cells orWe investigated the mechanisms of hematopoietic disorders caused by iron overload and chelation, in particular, the inhibition of erythroblast differentiation. Murine c-kit(+) progenitor cells or human CD34(+) peripheral blood hematopoietic progenitors were differentiated in vitro to the erythroid lineage with free iron and/or an iron chelator. Under iron overload, formation of erythroid burst-forming unit colonies and differentiation to mature erythroblasts were significantly suppressed; these effects were canceled by iron chelation with deferoxamine (DFO). Moreover, excessive iron burden promoted apoptosis in immature erythroblasts by elevating intracellular reactive oxygen species (ROS). Interestingly, both DFO and a potent anti-oxidant agent reduced intracellular ROS levels and suppressed apoptosis, thus restoring differentiation to mature erythroblasts. Accordingly, intracellular ROS may represent a new therapeutic target in the treatment of iron overload.

• AML1/RUNX1 functions as a cytoplasmic attenuator of NF-κB signaling in the repression of myeloid tumors.

  Authors: Masahiro Nakagawa, Munetake Shimabe, Naoko Watanabe-Okochi, Shunya Arai, Akihide Yoshimi, Akihito Shinohara, Nahoko Nishimoto, Keisuke Kataoka, Tomohiko Sato, Keiki Kumano, Yasuhito Nannya, Motoshi Ichikawa, Yoichi Imai, Mineo Kurokawa

  Blood. 12/2011; 118(25):6626-37.

  Functional deregulation of transcription factors has been found in many types of tumors. Transcription factor AML1/RUNX1 is one of the most frequent targets of chromosomal abnormalities in humanFunctional deregulation of transcription factors has been found in many types of tumors. Transcription factor AML1/RUNX1 is one of the most frequent targets of chromosomal abnormalities in human leukemia and altered function of AML1 is closely associated with malignant transformation of hematopoietic cells. However, the molecular basis and therapeutic targets of AML1-related leukemia are still elusive. Here, we explored immediate target pathways of AML1 by in vitro synchronous inactivation in hematopoietic cells. We found that AML1 inhibits NF-κB signaling through interaction with IκB kinase complex in the cytoplasm. Remarkably, AML1 mutants found in myeloid tumors lack the ability to inhibit NF-κB signaling, and human cases with AML1-related leukemia exhibits distinctly activated NF-κB signaling. Furthermore, inhibition of NF-κB signaling in leukemic cells with mutated AML1 efficiently blocks their growth and development of leukemia. These findings reveal a novel role for AML1 as a cytoplasmic attenuator of NF-κB signaling and indicate that NF-κB signaling is one of the promising therapeutic targets of hematologic malignancies with AML1 abnormality.

• Follicular lymphoma presenting with massive splenomegaly.

  Authors: Yosei Fujioka, Mineo Kurokawa

  International journal of hematology. 12/2011; 95(1):3-4.

• Pure red cell aplasia with follicular lymphoma showing regression and progression parallel to lymphoma.

  Authors: Go Yamamoto, Hiroaki Maki, Motoshi Ichikawa, Mineo Kurokawa

  International journal of hematology. 11/2011; 94(6):576-7.

• Lymphoma with specific affinity to endocrine organs.

  Authors: Ken Morita, Fumihiko Nakamura, Yasuhito Nannya, Yasuhiko Kamikubo, Motoshi Ichikawa, Mineo Kurokawa

  Annals of hematology. 11/2011;