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Aggressive NK cell leukemia

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https://www.readbyqxmd.com/read/28505169/molecular-basis-of-targeted-therapy-in-t-nk-cell-lymphoma-leukemia-a-comprehensive-genomic-and-immunohistochemical-analysis-of-a-panel-of-33-cell-lines
#1
Rufino Mondejar, Cristina Pérez, Arantza Onaindia, Nerea Martinez, Julia González-Rincón, Helena Pisonero, Jose Pedro Vaqué, Laura Cereceda, Miguel Santibañez, Margarita Sánchez-Beato, Miguel Angel Piris
T and NK-cell lymphoma is a collection of aggressive disorders with unfavorable outcome, in which targeted treatments are still at a preliminary phase. To gain deeper insights into the deregulated mechanisms promoting this disease, we searched a panel of 31 representative T-cell and 2 NK-cell lymphoma/leukemia cell lines for predictive markers of response to targeted therapy. To this end, targeted sequencing was performed alongside the expression of specific biomarkers corresponding to potentially activated survival pathways...
2017: PloS One
https://www.readbyqxmd.com/read/28485156/the-effects-of-lentivirus-mediated-shrna-interference-targeting-mcl-1-on-growth-of-nk-t-cell-lymphoma
#2
X Zhang, C Shi, G Yue, H Guo, X Fu, X Li, L Li, X Wang, Z Li, Y Chang, M Zhang, Q Chen
Myeloid leukemia-1 (Mcl-1) gene has been reported as an important factor in various types of cancer, but little research was processed on natural killer (NK)/T-cell lymphoma, a kind of a highly aggressive disease with a poor prognosis. Here we investigated the expression of Mcl-1 in seven lymphoma cell lines and its potential role as a molecular drug target for NK/T-cell lymphoma therapy by using lentivirus-mediated shRNA interference targeting Mcl-1 (lenti-shMcl-1). In our study, the expression of Mcl-1 in different lymphoma cell lines were evaluated firstly, after that lenti-shMcl-1 was constructed and transduced into NK/T-cell lymphoma cell line SNK-6 which had a high level expression of Mcl-1...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28346502/ebv-induces-persistent-nf-%C3%AE%C2%BAb-activation-and-contributes-to-survival-of-ebv-positive-neoplastic-t-or-nk-cells
#3
Honami Takada, Ken-Ichi Imadome, Haruna Shibayama, Mayumi Yoshimori, Ludan Wang, Yasunori Saitoh, Shin Uota, Shoji Yamaoka, Takatoshi Koyama, Norio Shimizu, Kouhei Yamamoto, Shigeyoshi Fujiwara, Osamu Miura, Ayako Arai
Epstein-Barr virus (EBV) has been detected in several T- and NK-cell neoplasms such as extranodal NK/T-cell lymphoma nasal type, aggressive NK-cell leukemia, EBV-positive peripheral T-cell lymphoma, systemic EBV-positive T-cell lymphoma of childhood, and chronic active EBV infection (CAEBV). However, how this virus contributes to lymphomagenesis in T or NK cells remains largely unknown. Here, we examined NF-κB activation in EBV-positive T or NK cell lines, SNT8, SNT15, SNT16, SNK6, and primary EBV-positive and clonally proliferating T/NK cells obtained from the peripheral blood of patients with CAEBV...
2017: PloS One
https://www.readbyqxmd.com/read/28194886/prognostic-significance-of-cytogenetic-abnormalities-in-t-cell-prolymphocytic-leukemia
#4
Zhihong Hu, L Jeffrey Medeiros, Lianghua Fang, Yi Sun, Zhenya Tang, Guilin Tang, Tsieh Sun, Andres E Quesada, Shimin Hu, Sa A Wang, Lin Pei, Xinyan Lu
T-cell prolymphocytic leukemia (T-PLL) is an aggressive mature T-cell neoplasm. The most common cytogenetic abnormality associated with T-PLL is inv(14)(q11.2q32) involving TCL1, but other abnormalities also have been reported. In this study, we correlated cytogenetic abnormalities with clinical outcome in 97 T-PLL patients, including 66 men and 31 women with a median age of 63 years (range, 34-81). Twenty-seven patients had a normal karyotype (NK), one had two chromosomal aberrations, and 69 had a complex karyotype (CK)...
February 14, 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28161608/allogeneic-hematopoietic-cell-transplantation-for-aggressive-nk-cell-leukemia-a-center-for-international-blood-and-marrow-transplant-research-analysis
#5
Mehdi Hamadani, Abraham S Kanate, Alyssa DiGilio, Kwang Woo Ahn, Sonali M Smith, Jong Wook Lee, Ernesto Ayala, Nelson Chao, Parameswaran Hari, Javier Bolaños-Meade, Ronald Gress, Niels Smedegaard Anderson, Yi-Bin Chen, Umar Farooq, Gary Schiller, Jean Yared, Anna Sureda, Timothy S Fenske, Horatiu Olteanu
Aggressive NK cell leukemia (ANKL) is an exceedingly rare form of leukemia and carries a poor prognosis, with a median survival of only 2 months. Using the Center for International Blood and Marrow Transplant Research database, we evaluated outcomes of allogeneic hematopoietic cell transplantation (alloHCT) in patients with ANKL. Twenty-one patients with a centrally confirmed diagnosis of ANKL were included. Median patient age was 42 years and 15 patients (71%) were Caucasian. Fourteen patients (67%) were in complete remission (CR) at the time of alloHCT, and 5 patients had active disease...
May 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#6
REVIEW
Thierry Lamy, Aline Moignet, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia has been recognized by the World Health Organization classifications amongst mature T-cell and natural killer (NK) cell neoplasms. There are 3 categories: chronic T-cell leukemia and NK-cell lymphocytosis, which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK-cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation, which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, phosphatidylinositol 3-kinase-Akt, Ras-Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid, and nuclear factor-κB...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28074066/preclinical-targeting-of-aggressive-t-cell-malignancies-using-anti-cd5-chimeric-antigen-receptor
#7
K H Chen, M Wada, K G Pinz, H Liu, K-W Lin, A Jares, A E Firor, X Shuai, H Salman, M Golightly, F Lan, L Senzel, E L Leung, X Jiang, Y Ma
The outlook for T-cell malignancies remain poor due to the lack of effective therapeutic options. Chimeric antigen receptor (CAR) immunotherapy has recently shown promise in clinical trials for B-cell malignancies, however, designing CARs for T-cell based disease remain a challenge due to the shared surface antigen pool between normal and malignant T-cells. Normal T-cells express CD5 but NK (natural killer) cells do not, positioning NK cells as attractive cytotoxicity cells for CD5CAR design. Additionally, CD5 is highly expressed in T-cell acute lymphoblastic leukemia (T-ALL) and peripheral T-cell lymphomas (PTCLs)...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28056294/-the-understanding-of-epstein-barr-virus-associated-lymphoproliferative-disorder
#8
X G Zhou, Y L Zhang, J L Xie, Y H Huang, Y Y Zheng, W S Li, H Chen, F Liu, H X Pan, P Wei, Z Wang, Y C Hu, K Y Yang, H L Xiao, M J Wu, W H Yin, K Y Mei, G Chen, X C Yan, G Meng, G Xu, J Li, S F Tian, J Zhu, Y Q Song, W J Zhang
In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases...
December 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/28054442/markers-and-function-of-human-nk-cells-in-normal-and-pathological-conditions
#9
REVIEW
Genny Del Zotto, Emanuela Marcenaro, Paola Vacca, Simona Sivori, Daniela Pende, Mariella Della Chiesa, Francesca Moretta, Tiziano Ingegnere, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta
Natural killer (NK) cells, the most important effectors of the innate lymphoid cells (ILCs), play a fundamental role in tumor immune-surveillance, defense against viruses and, in general, in innate immune responses. NK cell activation is mediated by several activating receptors and co-receptors able to recognize ligands on virus-infected or tumor cells. To prevent healthy cells from auto-aggression, NK cells are provided with strong inhibitory receptors (KIRs and NKG2A) which recognize HLA class I molecules on target cells and, sensing their level of expression, allow killing of targets underexpressing HLA-class I...
March 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27910003/bone-marrow-t-cell-percentage-a-novel-prognostic-indicator-in-acute-myeloid-leukemia
#10
Manar M Ismail, Nahla A B Abdulateef
Acute myeloid leukemia (AML) is an aggressive malignancy for which overall disease-free survival is less than 50%. Manipulation of the immune system is an interesting and promising therapy for AML patients. We aimed to characterize the immune system of AML patients, highlighting the clinical relevance of total bone marrow (BM) lymphocytes and subpopulations. Sixty-six new AML cases diagnosed according to WHO criteria from King Abdullah Medical City, KSA, from October 2012 to February 2015. Analysis of BM lymphocytes and subpopulations was done by flowcytometry...
April 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27830541/achievement-of-disease-control-with-donor-derived-eb-virus-specific-cytotoxic-t-cells-after-allogeneic-peripheral-blood-stem-cell-transplantation-for-aggressive-nk-cell-leukemia
#11
Shojiro Haji, Motoaki Shiratsuchi, Takamitsu Matsushima, Akiko Takamatsu, Mariko Tsuda, Yasuhiro Tsukamoto, Emi Tanaka, Hirofumi Ohno, Eriko Fujioka, Yuriko Ishikawa, Ken-Ichi Imadome, Yoshihiro Ogawa
Aggressive NK-cell leukemia (ANKL) is characterized by systemic infiltration of Epstein-Barr virus (EBV)-associated natural killer cells and poor prognosis. We report a case of ANKL in which EBV-specific cytotoxic T lymphocytes (CTLs) were induced. A 41-year-old male suffered from fever, pancytopenia, and hepatosplenomegaly. The number of abnormal large granular lymphocytes in the bone marrow was increased and the cells were positive for CD56 and EBV-encoded small nuclear RNAs. The patient was diagnosed with ANKL and achieved a complete response following intensive chemotherapy...
April 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27743148/t-cell-lymphomas-a-challenging-disease-types-treatments-and-future
#12
REVIEW
Helen Ma, Maher Abdul-Hay
T-cell lymphomas are rare and aggressive malignancies associated with poor outcome, often because of the development of resistance in the lymphoma against chemotherapy as well as intolerance in patients to the established and toxic chemotherapy regimens. In this review article, we discuss the epidemiology, pathophysiology, current standard of care, and future treatments of common types of T-cell lymphomas, including adult T-cell leukemia/lymphoma, angioimmunoblastic T-cell lymphoma, anaplastic large-cell lymphoma, aggressive NK/T-cell lymphoma, and cutaneous T-cell lymphoma...
February 2017: International Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27686672/a-screening-method-with-lymphocyte-percentage-and-proportion-of-granular-lymphocytes-in-the-peripheral-blood-for-large-granular-lymphocyte-lgl-leukemia
#13
Takahiro Tanahashi, Nodoka Sekiguchi, Kazuyuki Matsuda, Akihiro Matsumoto, Toshiro Ito, Hideyuki Nakazawa, Fumihiro Ishida
Large granular lymphocyte leukemia (LGL-L) is defined morphologically as a group of lymphoproliferative disorders, including T-cell large granular lymphocytic leukemia (T-LGL-L), chronic lymphoproliferative disorders of NK cells (CLPD-NK), and aggressive NK cell leukemia. We investigated the morphological features of LGL leukemic cells in LGL-L patients to identify screening methods best suited to application in daily clinical practice. LGL leukemic cells were mostly indistinguishable from normal LGL; however, we developed a simplified approach to distinguishing among these cells, in which lymphocyte  % and the proportion of granular lymphocytes among lymphocytes (GL %) can serve as parameters at the cut-off values of 52 and 50 %, respectively...
January 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/27631517/ebv-negative-aggressive-nk-cell-leukemia-lymphoma-clinical-pathologic-and-genetic-features
#14
Alina Nicolae, Karthik A Ganapathi, Trinh Hoc-Tran Pham, Liqiang Xi, Carlos A Torres-Cabala, Nahid M Nanaji, Hongbin D Zha, Zhen Fan, Sybil Irwin, Stefania Pittaluga, Mark Raffeld, Elaine S Jaffe
Aggressive natural killer cell leukemia (ANKL) is a systemic NK-cell neoplasm, almost always associated with Epstein-Barr virus (EBV). Rare cases of EBV-negative ANKL have been described, and some reports suggested more indolent behavior. We report the clinicopathologic, immunophenotypic, and molecular characteristics of 7 EBV-negative ANKL. All patients were adults, with a median age of 63 years (range 22 to 83 y) and an M:F ratio of 2.5:1. Five patients were White, 1 Black, and 1 Asian. All patients presented acutely, with fever (6/7), cytopenias (6/7), and splenomegaly (4/7)...
January 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27587245/-outcome-of-haploidentical-hematopoietic-stem-cell-transplantation-for-non-hodgkin-lymphoma
#15
T Xu, J Chen, Z M Jin, M Miao, C C Fu, H Y Qiu, X W Tang, Y Han, A N Sun, D P Wu
OBJECTIVE: To explore the efficacy and safety of haploidentical hematopoietic stem cell transplantation (Haplo- HSCT) for refractory, relapsed or highly aggressive non- Hodgkin lymphoma (NHL) patients. METHODS: A total of 26 patients with refractory, relapsed or highly aggressive NHL who received Haplo- HSCT from Jan. 2004 to Mar. 2015 were analyzed retrospectively. RESULTS: Of them, 4 patients had diffuse large B-cell lymphoma (DLBCL), 1 had follicular lymphoma, 5 had B-lymphoblastic lymphoma/leukemia, 9 had T- lymphoblastic lymphoma/leukemia, 1 patient anaplastic large cell lymphoma (ALK-negative), 5 had peripheral T-cell lymphoma (NOS), and 1 had NK/T-cell lymphoma...
August 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27566560/a-pyrazolo-3-4-d-pyrimidine-compound-inhibits-fyn-phosphorylation-and-induces-apoptosis-in-natural-killer-cell-leukemia
#16
Ilaria Laurenzana, Antonella Caivano, Stefania Trino, Luciana De Luca, Francesco La Rocca, Vittorio Simeon, Cristina Tintori, Francesca D'Alessio, Antonella Teramo, Renato Zambello, Antonio Traficante, Maddalena Maietti, Gianpietro Semenzato, Silvia Schenone, Maurizio Botta, Pellegrino Musto, Luigi Del Vecchio
Natural killer (NK) cell neoplasms are characterized by clonal proliferation of cytotoxic NK cells. Since there is no standard treatment to date, new therapeutic options are needed, especially for NK aggressive tumors. Fyn tyrosine kinase has a key role in different biological processes, such as cell growth and differentiation, being also involved in the pathogenesis of hematologic malignancies. Our previous studies led us to identify 4c pyrazolo[3,4-d]pyrimidine compound capable of inhibiting Fyn activation and inducing apoptosis in different cancer cell lines...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27494836/novel-anti-cd3-chimeric-antigen-receptor-targeting-of-aggressive-t-cell-malignancies
#17
Kevin H Chen, Masayuki Wada, Amelia E Firor, Kevin G Pinz, Alexander Jares, Hua Liu, Huda Salman, Marc Golightly, Fengshuo Lan, Xun Jiang, Yupo Ma
Peripheral T-cell lymphomas (PTCLS) comprise a diverse group of difficult to treat, very aggressive non-Hodgkin's lymphomas (NHLS) with poor prognoses and dismal patient outlook. Despite the fact that PTCLs comprise the majority of T-cell malignancies, the standard of care is poorly established. Chimeric antigen receptor (CAR) immunotherapy has shown in B-cell malignancies to be an effective curative option and this extends promise into treating T-cell malignancies. Because PTCLS frequently develop from mature T-cells, CD3 is similarly strongly and uniformly expressed in many PTCL malignancies, with expression specific to the hematological compartment thus making it an attractive target for CAR design...
August 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27456462/clinical-features-and-treatment-outcome-of-epstein-barr-virus-positive-nodal-t-cell-lymphoma
#18
Ki Sun Jung, Su-Hee Cho, Seok Jin Kim, Young Hyeh Ko, Won Seog Kim
The classification of mature NK-/T-cell lymphoma mainly originating from the T-cell lineage with predominantly nodal involvement and Epstein-Barr virus (EBV) positivity in a majority of tumor cells is unresolved. We analyzed the clinical features and treatment outcomes of such patients. Five patients with EBV-positive nodal T-cell lymphoma were surveyed during follow-up period. The median age was 53 years (range 33-88 years), and all patients showed nodal involvement. The patients mostly presented advanced clinical features, such as stage III or IV disease, elevated lactate dehydrogenase, and hemophagocytosis...
November 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27408372/cd56-negative-aggressive-t-cell-large-granular-lymphocytic-leukemia
#19
Mary Theresa Sylvia, Sajini Elizabeth Jacob, Debdatta Basu, Deepak Amalnath, Tarun Kumar Dutta
T cell large granular lymphocytic leukemia is a clonal proliferation of cytotoxic large granular T cells positive for CD3 and CD8. It is a chronic lymphoproliferative disorder with an indolent course. Therapeutic options include observation and low dose chemotherapy. Rarely, they have an aggressive course. Such cases have expression of NK cell associated antigens like CD56 in the T cells. These cases require more aggressive therapy with acute lymphoblastic leukemia regimens. We report a case of fatal CD56 negative T cell large granular lymphocytic leukemia in a 38 year old lady...
June 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/27178691/cutaneous-manifestations-and-management-of-hematologic-neoplasms
#20
REVIEW
Olalekan O Oluwole, John A Zic, Jonathan J Douds, Mary Ann Thompson, John P Greer
Many malignant hematologic neoplasms can directly and indirectly involve the skin with lesions that are disfiguring, painful, and compromise integumentary function. The majority of lymphomas that directly infiltrate the skin are of T-cell origin but B-cell lymphomas, and other hematologic neoplasms, including acute myeloid and lymphoblastic leukemias, can also have cutaneous involvement, whereas some have an indolent course, eg, mycosis fungoides and marginal zone lymphoma, and easily respond to localized therapy with overall survival (OS) measured in years to decades...
June 2016: Seminars in Oncology
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