WordNet

having or showing determination and energetic pursuit of your ends; "an aggressive businessman"; "an aggressive basketball player"; "he was aggressive and imperious; positive in his convictions"; "aggressive drivers"
characteristic of an enemy or one eager to fight; "aggressive acts against another country"; "a belligerent tone" (同)belligerent
tending to spread quickly; "an aggressive tumor" (同)fast-growing, strong-growing
small room in which a monk or nun lives (同)cubicle
a device that delivers an electric current as the result of a chemical reaction (同)electric cell
a room where a prisoner is kept (同)jail cell, prison cell
(biology) the basic structural and functional unit of all organisms; they may exist as independent units of life (as in monads) or may form colonies or tissues as in higher plants and animals
any small compartment; "the cells of a honeycomb"
a small unit serving as part of or as the nucleus of a larger political movement (同)cadre
malignant neoplasm of blood-forming tissues; characterized by abnormal proliferation of leukocytes; one of the four major types of cancer (同)leukaemia, leucaemia, cancer of the blood
the 14th letter of the Roman alphabet (同)n

PrepTutorEJDIC

侵略的な,攻撃的な / 積極的な,反対を恐れない
(刑務所の)『独房』;(修道院の)小さい独居室 / (ミツバチの)みつ房,巣穴 / 小さい部屋 / 『細胞』 / 電池 / 花粉室 / (共産党などの)細胞
白血病
nitrogenの化学記号

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/08/16 20:01:18」(JST)

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Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.^[1] ^[2] ^[3]

It is also called aggressive NK-cell lymphoma, or large granular lymphocyte leukemia, NK-cell type^[4]

Epidemiology[edit source | edit]

This rare form a leukemia is more common among Asians in comparison to other ethnic groups. It is typically diagnosed in adolescents and young adults, with a slight predominance in males.^[1]^[2]^[3]^[5] ^[6] ^[7] ^[8]

Clinical features[edit source | edit]

Etiology[edit source | edit]

This disease has a strong association with the Epstein-Barr virus (EBV),^[7] but the true pathogenesis of this disease has yet to be described. The cell of origin is believed to be an NK cell.^[4] Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.^[1]

Presentation[edit source | edit]

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure.^[1]^[2]^[5] ^[9] ^[10]

Laboratory findings[edit source | edit]

Leukemic cells are invariably present in samples of peripheral blood to a variable extent. Pancytopenia (anemia, neutropenia, thrombocytopenia) is commonly seen as well.^[4]

Sites of involvement[edit source | edit]

This disease is typically found and diagnosed in peripheral blood, and while it can involve any organ, it is usually found in the spleen, liver, and bone marrow.^[4]

Morphology[edit source | edit]

Peripheral blood[edit source | edit]

The leukemic cells have a diameter mildly greater than a large granular lymphocyte (LGL) and have azurophilic granules and nucleoli of varying prominence. Nuclei may be irregular and hyperchromatic.^[4]

Bone marrow[edit source | edit]

Bone marrow involvement runs the spectrum between an inconspicuous infiltrate to extensive marrow replacement by leukemic cells. Reactive histiocytes displaying hemophagocytosis can been seen interspersed in the neoplastic infiltrate.^[4]

Other organs[edit source | edit]

Leukemic involvement of organs is typically destructive on tissue sections with necrosis and possibly angioinvasion, and the monotonous infiltrate may be diffuse or patchy.^[4]

Molecular findings[edit source | edit]

Immunophenotype[edit source | edit]

The immunophenotype of this disease is the same as extranodal NK/T-cell lymphoma, nasal type and is shown in the table below. CD11b and CD16 show variable expression.^[1]^[8]

Status	Antigens
Positive	CD2, CD3ε, CD56, perforin, granzyme B, TIA-1, CCR5
Negative	CD57

Genetic findings[edit source | edit]

Due to the NK lineage, clonal rearrangements of lymphoid (T cell receptor; B cell receptor) genes are not seen.^[4] The genome of the Epstein Barr virus (EBV) is detected in many cases,^[7] along with a variety of chromosomal abnormalities.^[11]

Treatment[edit source | edit]

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant.^[12]^[13]^[14]^[15]^[16]^[17]^[18]^[19] Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

Pralatrexate is one compound currently under investigations for the treatment of PTCL. For information please consult the US clinical trials database (http://www.clinicaltrials.gov).

References[edit source | edit]

^ ^a ^b ^c ^d ^e Chan JK, Sin VC, Wong KF, et al. (June 1997). "Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm". Blood 89 (12): 4501–13. PMID 9192774.
^ ^a ^b ^c Imamura N, Kusunoki Y, Kawa-Ha K, et al. (May 1990). "Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells". Br. J. Haematol. 75 (1): 49–59. doi:10.1111/j.1365-2141.1990.tb02615.x. PMID 2375924.
^ ^a ^b Chan JK (1998). "Natural killer cell neoplasms". Anat Pathol 3: 77–145. PMID 10389582.
^ ^a ^b ^c ^d ^e ^f ^g ^h Elaine Sarkin Jaffe, Nancy Lee Harris, World Health Organization, International Agency for Research on Cancer, Harald Stein, J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors 3. Lyon: IARC Press. ISBN 92-832-2411-6.
^ ^a ^b Kwong YL, Wong KF, Chan LC, et al. (January 1995). "Large granular lymphocyte leukemia. A study of nine cases in a Chinese population". Am. J. Clin. Pathol. 103 (1): 76–81. PMID 7817949.
^ Kwong YL, Chan AC, Liang RH (May 1997). "Natural killer cell lymphoma/leukemia: pathology and treatment". Hematol Oncol 15 (2): 71–9. doi:10.1002/(SICI)1099-1069(199705)15:2<71::AID-HON601>3.0.CO;2-U. PMID 9375032.
^ ^a ^b ^c Gelb AB, van de Rijn M, Regula DP, et al. (September 1994). "Epstein-Barr virus-associated natural killer-large granular lymphocyte leukemia". Hum. Pathol. 25 (9): 953–60. doi:10.1016/0046-8177(94)90018-3. PMID 8088773.
^ ^a ^b Oshimi K (June 1996). "Lymphoproliferative disorders of natural killer cells". Int. J. Hematol. 63 (4): 279–90. doi:10.1016/0925-5710(96)00450-1. PMID 8762811.
^ Kobayashi Y, Uehara S, Inamori K, et al. (August 1996). "Hemophagocytosis as a para-neoplastic syndrome in NK cell leukemia". Int. J. Hematol. 64 (2): 135–42. doi:10.1016/0925-5710(96)00477-X. PMID 8854571.
^ Okuda T, Sakamoto S, Deguchi T, et al. (December 1991). "Hemophagocytic syndrome associated with aggressive natural killer cell leukemia". Am. J. Hematol. 38 (4): 321–3. doi:10.1002/ajh.2830380412. PMID 1746541.
^ Wong KF, Zhang YM, Chan JK (July 1999). "Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia—is there a consistent pattern?". Leuk. Lymphoma 34 (3–4): 241–50. doi:10.3109/10428199909050949. PMID 10439361.
^ Reimer P, Rüdiger T, Geissinger E, et al. (January 2009). "Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study". J. Clin. Oncol. 27 (1): 106–13. doi:10.1200/JCO.2008.17.4870. PMID 19029417.
^ Mercadal S, Briones J, Xicoy B, et al. (May 2008). "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma". Ann. Oncol. 19 (5): 958–63. doi:10.1093/annonc/mdn022. PMID 18303032.
^ Rodríguez J, Conde E, Gutiérrez A, et al. (July 2007). "Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group". Eur. J. Haematol. 79 (1): 32–8. doi:10.1111/j.1600-0609.2007.00856.x. PMID 17598836.
^ Corradini P, Tarella C, Zallio F, et al. (September 2006). "Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation". Leukemia 20 (9): 1533–8. doi:10.1038/sj.leu.2404306. PMID 16871285.
^ d’Amore F, et al. Blood. 2006;108:A401
^ Gisselbrecht C, Lepage E, Molina T, et al. (May 2002). "Shortened first-line high-dose chemotherapy for patients with poor-prognosis aggressive lymphoma". J. Clin. Oncol. 20 (10): 2472–9. doi:10.1200/JCO.2002.02.125. PMID 12011124.
^ Deconinck E, Lamy T, Foussard C, et al. (June 2000). "Autologous stem cell transplantation for anaplastic large-cell lymphomas: results of a prospective trial". Br. J. Haematol. 109 (4): 736–42. doi:10.1046/j.1365-2141.2000.02098.x. PMID 10929023.
^ Haioun C, Lepage E, Gisselbrecht C, et al. (August 2000). "Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphoma: final analysis of the prospective LNH87-2 protocol--a groupe d'Etude des lymphomes de l'Adulte study". J. Clin. Oncol. 18 (16): 3025–30. PMID 10944137.

UpToDate Contents

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1. ナチュラルキラー（NK）細胞大顆粒リンパ球性白血病 natural killer nk cell large granular lymphocyte leukemia
2. 造血腫瘍の分類 classification of the hematopoietic neoplasms
3. 大顆粒T細胞リンパ球性白血病の臨床症状、病理学的特徴、および診断 clinical manifestations pathologic features and diagnosis of t cell large granular lymphocyte leukemia
4. NK細胞欠損症候群：臨床症状および診断 nk cell deficiency syndromes clinical manifestations and diagnosis
5. 関節リウマチにおける大顆粒リンパ球性白血病 large granular lymphocyte leukemia in rheumatoid arthritis

English Journal

Cytotoxic human peripheral blood-derived γδT cells kill glioblastoma cell lines: implications for cell-based immunotherapy for patients with glioblastoma.

Nakazawa T, Nakamura M, Park YS, Motoyama Y, Hironaka Y, Nishimura F, Nakagawa I, Yamada S, Matsuda R, Tamura K, Sugimoto T, Takeshima Y, Marutani A, Tsujimura T, Ouji N, Ouji Y, Yoshikawa M, Nakase H.Author information Department of Neurosurgery, Nara Medical University School of Medicine, 840, Shijocho, Kashihara, Nara, 634-8522, Japan, nakazawa@naramed-u.ac.jp.AbstractGlioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated killing. To investigate the feasibility of γδT cell-based immunotherapy for patients with GBM, we focused on the killing of GBM cell lines by γδT cells and the molecular mechanisms involved in these cell-cell interactions. Peripheral blood mononuclear cells were expanded in ZOL and interleukin (IL)-2 for 14 days, and γδT cells were enriched in the expanded cells by the immunomagnetic depletion of αβT cells. Gliomas are resistant to NK cells but susceptible to lymphokine-activated killer cells and some cytotoxic T lymphocytes. When the γδT cell-mediated killing of three GBM cell lines (U87MG, U138MG and A172 cells) and an NK-sensitive leukemia cell line (K562 cells) were tested, 32 % U87MG, 15 % U138MG, 1 % A172, and 50 % K562 cells were killed at an effector:target ratio of 5:1. The γδT cell-mediated killing of all three GBM cell lines was significantly enhanced by ZOL and this ZOL-enhanced killing was blocked by an anti-T cell receptor (TcR) antibody. These results indicated that TcR γδ is crucial for the recognition of ZOL-treated GBM cells by γδT cells. Since the low level killing of GBM cells by the γδT cells was enhanced by ZOL, γδT cell-targeting therapy in combination with ZOL treatment could be effective for patients with GBM.
Journal of neuro-oncology.J Neurooncol.2014 Jan;116(1):31-9. doi: 10.1007/s11060-013-1258-4. Epub 2013 Sep 24.
Glioblastoma (GBM) is a highly aggressive brain tumor for which novel therapeutic approaches, such as immunotherapy, are urgently needed. Zoledronate (ZOL), an inhibitor of osteoclastic activity, is known to stimulate peripheral blood-derived γδT cells and sensitize tumors to γδT cell-mediated k
PMID 24062140

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Rapidly Progressive and Fatal Disease without Aggressive Intervention.

Prochaska L1, Dakhil C2, Mathur S3.Author information 1Resident Physician, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, USA.2Hematology/Oncology Fellow, Department of Internal Medicine, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS, USA.3Pathologist, Department of Pathology and Laboratory Medicine, Kansas City VA Medical Center, 4801 East Linwood Boulevard, Kansas City, MO, USA.AbstractBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid neoplasm derived from plasmacytoid monocytes. The most common presentation involves cutaneous manifestations, which are often accompanied by bone marrow involvement. The tumor cells reveal an immature blastic appearance and diagnosis is based on the expression of cluster of differentiation (CD)4 and CD56. The literature reports a high relapse rate and poor prognosis when treated with leukemia-type induction chemotherapy alone; however, long-term remission is attainable with allogeneic stem cell transplantation in the first complete remission. Here, we report the dismal course of a patient with BPDCN with cutaneous and bone marrow involvement unable to undergo an aggressive intervention.
Clinical medicine insights. Case reports.Clin Med Insights Case Rep.2013 Dec 18;6:201-4. doi: 10.4137/CCRep.S12608.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid neoplasm derived from plasmacytoid monocytes. The most common presentation involves cutaneous manifestations, which are often accompanied by bone marrow involvement. The tumor cells reveal an immature blastic appearance an
PMID 24385715

An intact immune system is required for the anticancer activities of histone deacetylase inhibitors.

West AC, Mattarollo SR, Shortt J, Cluse LA, Christiansen AJ, Smyth MJ, Johnstone RW.Author information Authors' Affiliations: Cancer Therapeutics Program, and Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria; The University of Queensland Diamantina Institute, Translational Research Institute, Woolloongabba; Queensland Institute of Medical Research; and School of Medicine, University of Queensland, Herston, Queensland, Australia.AbstractCell-intrinsic effects such as induction of apoptosis and/or inhibition of cell proliferation have been proposed as the major antitumor responses to histone deacetylase inhibitors (HDACi). These compounds can also mediate immune-modulatory effects that may contribute to their anticancer effects. However, HDACi can also induce anti-inflammatory, and potentially immunosuppressive, outcomes. We therefore sought to clarify the role of the immune system in mediating the efficacy of HDACi in a physiologic setting, using preclinical, syngeneic murine models of hematologic malignancies and solid tumors. We showed an intact immune system was required for the robust anticancer effects of the HDACi vorinostat and panobinostat against a colon adenocarcinoma and two aggressive models of leukemia/lymphoma. Importantly, although HDACi-treated immunocompromised mice bearing established lymphoma succumbed to disease significantly earlier than tumor bearing, HDACi-treated wild-type (WT) mice, treatment with the conventional chemotherapeutic etoposide equivalently enhanced the survival of both strains. IFN-γ and tumor cell signaling through IFN-γR were particularly important for the anticancer effects of HDACi, and vorinostat and IFN-γ acted in concert to enhance the immunogenicity of tumor cells. Furthermore, we show that a combination of vorinostat with α-galactosylceramide (α-GalCer), an IFN-γ-inducing agent, was significantly more potent against established lymphoma than vorinostat treatment alone. Intriguingly, B cells, but not natural killer cells or CD8(+) T cells, were implicated as effectors of the vorinostat antitumor immune response. Together, our data suggest HDACi are immunostimulatory during cancer treatment and that combinatorial therapeutic regimes with immunotherapies should be considered in the clinic. Cancer Res; 73(24); 7265-76. ©2013 AACR.
Cancer research.Cancer Res.2013 Dec 15;73(24):7265-76. doi: 10.1158/0008-5472.CAN-13-0890. Epub 2013 Oct 24.
Cell-intrinsic effects such as induction of apoptosis and/or inhibition of cell proliferation have been proposed as the major antitumor responses to histone deacetylase inhibitors (HDACi). These compounds can also mediate immune-modulatory effects that may contribute to their anticancer effects. How
PMID 24158093

Japanese Journal

NK細胞腫瘍の診断と治療における最近の進歩

臨床血液 56(6), 645-650, 2015
NAID 130005093098

アグレッシブNK細胞白血病の臨床病態と治療

血液内科 68(1), 124-128, 2014-01
NAID 40019971835

Spontaneous Regression of Cutaneous Blastic Plasmacytoid Dendritic Cell Neoplasm Followed by Acute Monocytic Leukemia Evolving from Myelodysplastic Syndrome