Tomoaki Akagi

A novel gene, MALT1 at 18q21, is involved in t(11;18) (q21;q21) found in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

The t(11;18) (q21;q21) translocation is a characteristic chromosomal aberration in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. We previously identified a YAC clone y789F3, which includes the breakpoint at 18q21 in a MALT lymphoma patient. BAC and PAC contigs were constructed on the YAC, and BAC 193f9 was found to encompass the breakpoint region. In the present study, we further narrowed down the breakpoint region at 18q21 in five MALT lymphoma patients by means of FISH and Southern blot analyses using the plasmid contig constructed from BAC 193f9. The breakpoints at 18q21 in three of the five MALT lymphoma patients were found to be clustered approximately within the 20 kb region. By using exon amplification and cDNA library screening, we identified a novel cDNA spanning the breakpoint region that exhibited aberrant mRNA signals in four of the five MALT lymphoma patients. The nucleotide sequence predicted an 813 amino acid protein that shows significant sequence similarity to the CD22β and laminin 5 α3b subunit. We refer to the gene encoding this transcript as MALT1 (Mucosa-Associated Lymphoid Tissue lymphoma translocation gene 1). The alteration of MALT1 by translocation strongly suggests that this gene plays an important role in the pathogenesis of MALT lymphoma.

Molecular cytogenetic delineation of the breakpoint at 18q21.1 in low-grade B-cell lymphoma of mucosa-associated lymphoid tissue.

Extranodal malignant non‐Hodgkin lymphoma of mucosa‐associated lymphoid tissue type (MALT lymphoma) represents a subtype of B‐cell lymphoid malignancies with distinct clinicopathological features and is often associated with a favorable prognosis. Recent cytogenetic studies have revealed that t(11;18)(q21;q21) is a characteristic chromosomal aberration in low‐grade B‐cell MALT‐type lymphoma. In the present study, we employed florescence in situ hybridization analysis using contiguous YAC clones mapped to the 18q21.1 region to identify a YAC clone, y789F3, encompassing the breakpoint of t(11;18)(q21;q21) in a MALT lymphoma. P1 artificial chromosome (PAC) contigs constructed on this YAC clone were used to analyze the breakpoint region. PAC clone 264m4 was observed on normal chromosome 18 and on der(18), and PAC clone 879n10 on normal chromosome 18 and on der(11), confirming that the breakpoint is located between these two PAC clones. We also found that a region of approximately 500 kb between the two PAC clones was deleted. These results indicate that the locus between PAC clones 264m4 and 879n10 at 18q21.1 involved in t(11;18) translocation or associated deletion plays an important role in the development of MALT lymphoma. Genes Chromosomes Cancer 24:315–321, 1999.

Breakthrough trichosporonosis in patients with acute myeloid leukemia receiving micafungin

Echinocandins are a new class of antifungal compounds. Micafungin, an agent of this class, inhibits the synthesis of 1,3-b-D-glucan, an essential fungal cellwall component. Micafungin has activity against a broad spectrum of fungi, including molds such as Aspergillus species and most yeast species; however, it is not active against Trichosporon species [1]. Trichosporon species, usually found in fresh water, have also been recovered from normal skin and oral micro-flora [2]. These fungi are known to cause white piedra, hyper sensitive pneumonia and invasive infection in immunocompromised patients [3]. We report two cases of Trichosporon asahii fungemia in patients with acute myeloblastic leukemia (AML), both of whom received micafungin as a single agent for anti-fungal prophylaxis. A 79-year-old woman was admitted to our hospital in March 2003 with a diagnosis of AML (M2 in FAB classification). Her pulmonary examination was normal. Tests for Aspergillus and Candida antigens were negative and serum 1,3-b-D-glucan, a marker of fungal infection, was also negative. Treatment with a granulocyte-colony stimulating factor, aclarubicin, and cytosine arabinoside was started. On the fifth day after initiation of chemotherapy, her absolute neutrophil count (ANC) declined to 100 mL. Treatment with imipenem/cilastatin 1 g per day and micafungin 75 mg per day was started. On the 14 day, she developed symptoms of chest pain and a temperature of 398C. A chest radiograph revealed pneumonia in the upper right pulmonary lobe. Serum 1,3-b-D-glucan was elevated at 81.1 pg ml (normal520). Blood culture yielded Trichosporon species; fungal identification revealed Trichosporon asahii. She was switched from micafungin to fluconazole (400 mg per day) and granulocyte-colony stimulating factor (300 mg per day) was added. Five days later, the patient’s neutrophil count was greater than 1000 mL, her fever was reduced and her condition improved dramatically. A 72-year-old man was referred in June 2003 with a diagnosis of AML (M1 in FAB classification). On admission to our hospital, physical examination revealed osteomyelitis of the mandible, an inflammatory lesion caused by dental caries. He also had a temperature of 398C. Blood culture taken prior to antibiotic therapy was negative. Tests for Aspergillus and Candida antigens and serum 1,3-D-glucan were also negative. Initial laboratory tests revealed a neutrophil count of only 100 mL. Treatment with imipenem/cilastatin 1 g per day and micafungin 75 mg per day were started. The patient’s fever decreased after 7 days. He underwent induction chemotherapy with daunorubicin and cytosine arabinoside. On the 14 day after the start of chemotherapy, a septic syndrome appeared, with alternating fever and chills. A chest radiograph revealed bilateral lung infiltrates with a reticulonodular pattern. Serum 1,3-b-D-glucan was elevated at 97.6 pg ml (normal5 20). Blood culture was positive for Trichosporon species; fungal identification revealed

Delineation of the breakpoint at 18q21.1 in a cell line (KARPAS1106) derived from mediastinal B‐cell lymphoma by fluorescencein situ hybridization with multiple YAC clones

The breakpoint of the 18q21 translocation of B‐cellnon‐Hodgkins lymphoma (NHL) cell line Karpas1106P was delineated by fluorescence in situ hybridization (FISH). Karpas1106P was derived from mediastinal lymphoblastic B‐cell lymphoma and exhibited the immunophenotype characteristic of marginal‐zone B‐cell lymphoma (MZL): smIg+, pan‐B antigen+, CD5−, CD10− and CD23−. The original G‐banded karyotype showed a complex translocation containing t(X;18;13)(q28;q21;q12.1). Double‐color FISH (DCFISH) with whole‐chromosome‐painting (WCP) probes for chromosomes X, 13 and 18, and 18q‐specific yeast artificial chromosome (YAC) clones defined t(X;18;13) as ider(X)t(X;18;13)(q28;q12.3q21.1;q12.1). The immunoglobulin‐heavy‐chain (IgH) gene was not involved in the chromosomal translocation as detected by DCFISH with VH and Cγ probes. By using contiguous YAC clones mapped from 18q12.3 to q21.1, we identified a YAC clone y852H2 with its breakpoint at 18q21.1. In Karpas1106P, the distal part of chromosome 18 from the breakpoint (18q21.1‐qter) was deleted, showing loss of heterozygosity of this region. In addition, the chromosomal segment 18q21.1 was duplicated and inserted to ider(X)t(X;18;13) between Xq28 and 13q12.1 with maintaining its original orientation. The DNA sequence of the breakpoint region contained in y852H2 can serve as a candidate locus for further molecular dissection to identify the causative gene of MZL. Int. J. Cancer 78:100–105, 1998.© 1998 Wiley‐Liss, Inc.

Comparison of micafungin and voriconazole as empirical antifungal therapies in febrile neutropenic patients with hematological disorders: a randomized controlled trial.

In cases of hematological malignancy, patients with persistent fever and neutropenia receive antifungal empirical therapy to prevent and treat invasive fungal infections. The clinical efficacy and safety of micafungin and voriconazole were compared.

High prevalence of diffuse large B-cell lymphoma in occult hepatitis B virus-infected patients in the Tohoku district in Eastern Japan.

Occult hepatitis B virus (HBV) infection is a clinical challenge, but its relationship to clinicopathologic features and the risk of progression to malignant lymphoma (ML) are poorly defined. We estimated the prevalence of HBV infection of 1,358 patients with newly diagnosed ML. HBV infection was more prevalent in ML than in control patients. The occult HBV infection group had a higher median onset age, no liver or spleen involvement, and higher prevalence of diffuse large B‐cell lymphoma than the other groups, indicating that occult HBV infection is a distinct clinicopathologic entity. J. Med. Virol. 88:2206–2210, 2016.

A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria.

We conducted a phase II study to evaluate the efficacy and safety of dasatinib in Japanese patients with imatinib‐resistant or imatinib‐intolerant chronic myeloid leukemia (CML).

Clinicopathological characteristics of malignant lymphoma in patients with hepatitis C virus infection in the Tohoku district in Eastern Japan

Katsushi Tajima, Naoto Takahashi, Kenichi Ishizawa, Kazunori Murai, Tomoaki Akagi, Hideyoshi Noji, Osamu Sasaki, Masaharu Wano, Jugoh Itoh, Yuichi Kato, Tsutomu Shichishima, Hideo Harigae and Yoji Ishida: for the Tohoku Hematology Forum Department of Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba, Japan; Department of Neurology, Hematology, Metabolism, Endocrinology, and Diabetology, Yamagata University School of Medicine, Yamagata, Japan; Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Akita, Japan; Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Hematology/ Oncology, Internal Medicine, Iwate Medical University, Morioka, Japan; Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan; Division of Hematology, Department of Internal Medicine, Miyagi Cancer Center, Natori, Japan; Department of Hematology, Iwate Prefectural Hospital, Morioka, Japan; Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

Suspected Pulmonary Infection with Trichoderma longibrachiatum after Allogeneic Stem Cell Transplantation.

Aspergillus and Candida species are the main causative agents of invasive fungal infections in immunocompromised human hosts. However, saprophytic fungi are now increasingly being recognized as serious pathogens. Trichoderma longibrachiatum has recently been described as an emerging pathogen in immunocompromised patients. We herein report a case of isolated suspected invasive pulmonary infection with T. longibrachiatum in a 29-year-old man with severe aplastic anemia who underwent allogeneic stem cell transplantation. A direct microscopic examination of sputum, bronchoaspiration, and bronchoalveolar lavage fluid samples revealed the presence of fungal septate hyphae. The infection was successfully treated with 1 mg/kg/day liposomal amphotericin B.