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Volume 56, Issue 12
Displaying 1-15 of 15 articles from this issue
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[in Japanese], [in Japanese], [in Japanese], [in Japanese], [in Japane ...2015 Volume 56 Issue 12 Pages 2417
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSDownload PDF (1285K)
The 75th Annual Meeting of the Japanese Society of Hematology
Special Award Received Lecture
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Norio SHIBA2015 Volume 56 Issue 12 Pages 2419-2425
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA new class of gene mutations, identified in the pathogenesis of adult acute myeloid leukemia (AML), includes DNMT3A, IDH1/2, TET2 and EZH2. However, these mutations are rare in pediatric AML cases, indicating that pathogeneses differ between adult and pediatric forms of AML. Meanwhile, the recent development of massively parallel sequencing technologies has provided a new opportunity to discover genetic changes across entire genomes or proteincoding sequences. In order to reveal a complete registry of gene mutations, we performed whole exome resequencing of paired tumor-normal specimens from 19 pediatric AML cases using Illumina HiSeq 2000. In total, 80 somatic mutations or 4.2 mutations per sample were identified. Many of the recurrent mutations identified in this study involved previously reported targets in AML, such as FLT3, CEBPA, KIT, CBL, NRAS, WT1 and EZH2. On the other hand, several genes were newly identified in the current study, including BCORL1 and major cohesin components such as SMC3 and RAD21. Whole exome resequencing revealed a complex array of gene mutations in pediatric AML genomes. Our results indicate that a subset of pediatric AML represents a discrete entity that could be discriminated from its adult counterpart, in terms of the spectrum of gene mutations.View full abstractDownload PDF (2031K) -
Masayuki YAMASHITA, Eriko NITTA, Toshio SUDA2015 Volume 56 Issue 12 Pages 2426-2433
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSHematopoietic stem cells (HSCs) are predominantly in a quiescent state, thereby avoiding depletion due to various stresses. However, quiescent HSCs are vulnerable to mutagenesis due to low-fidelity DNA repair. The mechanism by which HSCs avoid mutation accumulation remains to be elucidated. HSCs are normally resistant to apoptosis because of their abundant expressions of pro-survival Bcl-2 family genes. In contrast, p53 is activated in HSCs in response to DNA damage. We have recently shown that pro-apoptotic Bcl-2 signals are activated through p53 preferentially in HSCs with damaged DNA. Aspp1, an apoptosis-stimulating protein of p53, is highly expressed in HSCs and coordinates with p53 to maintain the genomic soundness of the HSC pool. In this review, we will summarize apoptosis regulation and the roles of p53 in HSCs, and introduce our findings showing coordinated regulations of HSC self-renewal, DNA damage tolerance and hematological malignancies by Aspp1 and p53.View full abstractDownload PDF (1335K) -
Satoshi SAIDA2015 Volume 56 Issue 12 Pages 2434-2440
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSLeukemia arises through an evolutionary process of somatic mutation and selection. Transient abnormal myelopoiesis (TAM) is a clonal pre-leukemic disorder that progresses to myeloid leukemia of Down syndrome (ML-DS) through the accumulation of genetic alterations. To investigate the mechanism underlying leukemogenesis, a xenograft model of TAM was established using NOG mice. Serial engraftment after cell transplantation from a TAM patient who developed ML-DS a year later showed the self-renewal capacity of these cells. We detected a GATA1 mutation but no copy number alterations (CNAs) in the primary patient sample by conventional genomic sequencing and CNA profiling. However, engrafted TAM-derived cells showed the emergence of divergent subclones with another GATA1 mutation and various CNAs, including a 16q deletion and 1q gain, both of which are clinically associated with ML-DS. Detailed genetic analysis identified minor subclones with a 16q deletion or this distinct GATA1 mutation in the primary patient sample. These results suggest that genetically heterogeneous subclones with various leukemia-initiating potentials already exist in the neonatal TAM phase, and that ML-DS may develop from a pool of such minor clones through clonal selection. Our xenograft model could be a valuable tool for gaining insight into the processes underlying leukemogenesis.View full abstractDownload PDF (2920K)
Case Reports
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Takuma ISHIZAKI, Takeki MITSUI, Yuri UCHIYAMA, Yoshiyuki OGAWA, Hiromi ...2015 Volume 56 Issue 12 Pages 2441-2446
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSAn 80-year-old man, presenting with gait disturbance and memory loss, had findings of normal pressure hydrocephalus. Primary leptomeningeal lymphoma (PLML) was diagnosed based on cytology and flow cytometry of cerebrospinal fluid obtained by examination. Gadolinium-enhanced MRI showed enhancement of the brain and spinal cord but FDG-PET/CT revealed no lymph node swelling. With intrathecal chemotherapy, meningeal lesions disappeared and the gait disturbance and memory loss improved. However, the disease recurred three months later, manifesting as left facial nerve palsy, but the symptoms disappeared in response to intrathecal chemotherapy and systemic rituximab administration. Although a tumor lesion in the spinal canal was suggested by MRI examination, the patient has maintained a good clinical course for four years with intrathecal chemotherapy every three months. PLML is a very rare disease and its diagnosis is difficult. Repeated intrathecal chemotherapy appeared to be effective against PLML in this case.View full abstractDownload PDF (1371K) -
Isao NAGASAKA, Takeki MITSUI, Takuma ISHIZAKI, Hiromi KOISO, Akihiko Y ...2015 Volume 56 Issue 12 Pages 2447-2451
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSTesticular lymphoma is a rare disease, accounting for 1-2% of non-Hodgkin lymphoma and 5-9% of all testicular tumors, and has a high relapse rate with a poor prognosis. We report a patient with testicular diffuse large B-cell lymphoma (DLBCL) who relapsed after being in remission for 16 years. He had undergone orchiectomy of the right testis and was diagnosed as having DLBCL (stage IAE) at 49 years of age. After 3 cycles of CHOP, he achieved a complete remission. Orchiectomy was performed because of a left testicular tumor, and he was again diagnosed with DLBCL at the age of 65. VH3-21 was detected in lymphoma cells at the times of both the first diagnosis and the relapse based on analysis of the variable region of the immunoglobulin heavy chain. Accordingly, the lymphoma cells at relapse were confirmed to be the same clone as that which had been documented at the first diagnosis.View full abstractDownload PDF (2759K) -
Takashi ONAKA, Tomoya KITAGAWA, Minako MORI, Akihito YONEZAWA, Kazunor ...2015 Volume 56 Issue 12 Pages 2452-2455
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 45-year-old man was diagnosed with t(8;21) positive acute myelogenous leukemia and failed to achieve complete remission (CR) after the first induction chemotherapy. He was then treated with high-dose cytarabine and achieved CR. Molecular relapse was detected during post-remission therapy and he underwent myeloablative bone marrow transplantation from his HLA-matched sibling donor. One year after transplantation, he developed an intractable anal fistula during treatment of chronic GVHD. Colonoscopy showed longitudinal ulcers and cobblestone appearance, and histopathological examination revealed non-caseating epithelioid granuloma. According to these findings, he was diagnosed with Crohn's-like chronic gastrointestinal inflammatory disease. He was treated with enteral nutrition, mesalazine and dose re-escalation of cyclosporine, but these therapies were not effective. Therefore, we decided to treat him with infliximab. After starting treatment with infliximab, his abdominal symptoms and the anal fistula showed prompt improvement. There are few reports regarding the efficacy of infliximab for gastrointestinal chronic GVHD. Our experience suggests that infliximab could be useful for the treatment of Crohn's-like gastrointestinal inflammatory disease.View full abstractDownload PDF (2335K) -
Kota HAMAGUCHI, Akari HASHIMOTO, Akihito FUJIMI, Yuji KANISAWA, Takano ...2015 Volume 56 Issue 12 Pages 2456-2461
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSAn 86-year-old man presented with enlarged left submandibular, left inguinal, and superficial femoral lymph nodes. He was diagnosed with Langerhans cell sarcoma (LCS) on the basis of the histopathological findings of the left inguinal lymph node biopsy. In addition, laboratory examinations revealed normocytic normochromic anemia, and bone marrow aspiration and biopsy led to a diagnosis of idiopathic cytopenia of undetermined significance (ICUS). Because of the patient's age, he was administered a regimen of cyclophosphamide, pirarubicin, vincristine, and prednisolone (THP-COP), and achieved a partial response after six courses. However, he developed acute myeloid leukemia (AML) 11 months after completion of the THP-COP therapy, and received only supportive care until his death. LCS is an extremely rare and aggressive dendritic cell neoplasm. To the best of our knowledge, only 67 cases have been reported in the literature. There are case reports describing the concurrence of hematological malignancies. Herein, we report the first documented development of LCS in a patient with ICUS who progressed to AML, and summarize the published data on the epidemiology of and therapeutic options for LCS.View full abstractDownload PDF (2035K) -
Akiko MASUDA, Masahiro JONA, Akira HONDA, Yumiko SATOH, Mineo KUROKAWA ...2015 Volume 56 Issue 12 Pages 2462-2466
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 64-year-old man was referred to our hospital because of mild anemia, erythroblasts in peripheral blood, and hyperferritinemia. In our hospital, no evidence of cytopenia was found. The peripheral blood smear showed pseudo-Pelger-Huët anomaly and giant platelets. The serum ferritin level was extremely high (1,405 ng/ml). A bone marrow examination was performed for further evaluation and revealed trilineage dysplasia. Since the patient did not fulfill the diagnostic criteria for cytopenias associated with myelodysplastic syndromes, he was diagnosed as having idiopathic dysplasia of undetermined/uncertain significance (IDUS). The SF3B1 mutation was identified in this patient, suggesting that he might be at a stage prior to myelodysplastic syndrome. Some IDUS patients reportedly progress to myeloid neoplasms, making careful observation essential. If morphological dysplasia in peripheral blood and hyperferritinemia are present, these findings suggest bone marrow failure syndromes. In such cases, further evaluation including a bone marrow examination may be required.View full abstractDownload PDF (2006K) -
Miwa KURIMOTO, Akihisa NAGATA, Naohiro SEKIGUCHI, Satoshi NOTO, Naoki ...2015 Volume 56 Issue 12 Pages 2467-2471
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 90-year-old woman was diagnosed with chronic myeloid leukemia (CML) of the high risk type (Sokal score 1.5), and was administered imatinib (400 mg/day). However, imatinib had to be switched to nilotinib because she suffered persistent vomiting and nausea. Although a cytogenetic response was achieved, the nilotinib administration also had to be stopped because the patient developed QTc prolongation and heart failure. After she had recovered from heart failure, the patient was given dasatinib (50 mg/day). No non-hematological adverse events occurred and she achieved a molecular response with administration of dasatinib. A molecular response can be achieved through appropriate supportive care and careful selection of tyrosine kinase inhibitors, with adjustments in the doses of these drugs administered to patients with the high-risk form of CML who are intolerant to imatinib.View full abstractDownload PDF (914K) -
Yuya SASAKI, Akihito YONEZAWA, Yoshihiro KINOSHITA, Tomoya KITAGAWA, M ...2015 Volume 56 Issue 12 Pages 2472-2476
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 66-year-old man showed central nervous system (CNS) and epididymis involvement after concurrent chemoradiotherapy for extranodal natural killer/T-cell lymphoma, nasal type (ENKL). The patient experienced continuous nasal obstruction. CT revealed a mass in the nasal cavity and paranasal sinuses. Biopsy of the nasal cavity mass showed it to be ENKL. Based on bone marrow biopsy and 18F-FDG PET/CT findings, the clinical stage was suspected to be IIE. The sites involved were the nasal cavity, paranasal sinuses, and cervical lymph nodes. We performed concurrent chemoradiotherapy consisting of a 67% dose of DeVIC and involved field radiation therapy towards his head and neck. Head and neck CT confirmed a therapeutic response. After receiving concurrent chemoradiotherapy, the patient complained of perineal discomfort. Ultrasonography revealed swelling of the left epididymis. Left epididymis biopsy showed ENKL involvement and lumbar puncture revealed CNS involvement. The findings of this case suggest that evaluation of CNS involvement might be an essential part of the initial workup for some ENKL patients.View full abstractDownload PDF (1868K) -
Yuki HIROSHIMA, Hiroko KAIUME, Takehiko KIRIHARA, Wataru TAKEDA, Taro ...2015 Volume 56 Issue 12 Pages 2477-2482
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.View full abstractDownload PDF (1370K) -
Hideaki OHYAGI, Masaaki KUME, Yoshinori SHINOHARA, Satsuki TAKAHASHI, ...2015 Volume 56 Issue 12 Pages 2483-2487
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSA 58-year-old woman was admitted to our hospital for evaluation of left flank pain. Abdominal computed tomography showed a greatly enlarged splenic tumor with a massive portal vein tumor thrombosis (PVTT). We suspected non-Hodgkin lymphoma (NHL) based on the high values of serum soluble interleukin-2 receptor and lactate dehydrogenase. Because there was no superficial lymph node enlargement, ultrasound-guided percutaneous trans-hepatic needle biopsy was performed to obtain a pathological diagnosis of PVTT, instead of a splenectomy, after the patient had provided informed consent. This procedure was thought to be less invasive than splenectomy. Histologic examination revealed CD20-positive NHL. A complete response was achieved after six courses of R-CHOP and it was confirmed by splenectomy. A PVTT due to NHL is extremely rare as compared with that due to hepatocellular carcinoma, gastric cancer, and colon cancer. However, NHL should be considered in the differential diagnosis for a patient with a PVTT, because B cell-NHL tends to have a good prognosis when rituximab combined chemotherapy is administered. We suggest that a percutaneous trans-hepatic needle biopsy may be useful for diagnosing PVTT due to NHL.View full abstractDownload PDF (1570K)
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2015 Volume 56 Issue 12 Pages 2520-2531
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSDownload PDF (849K)
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2015 Volume 56 Issue 12 Pages 2533
Published: 2015
Released on J-STAGE: December 29, 2015
JOURNAL RESTRICTED ACCESSDownload PDF (573K)
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