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LGL Leukemia

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https://www.readbyqxmd.com/read/29699990/trail-mediates-and-sustains-constitutive-nf-%C3%AE%C2%BAb-activation-in-lgl-leukemia
#1
Jun Yang, Francis R LeBlanc, Shubha A Dighe, Cait E Hamele, Thomas L Olson, David J Feith, Thomas P Loughran
Large granular lymphocyte (LGL) leukemia results from clonal expansion of CD3+ cytotoxic T-lymphocytes or CD3- natural killer (NK) cells. Chronic antigen stimulation is postulated to promote long-term survival of LGL leukemia cells through constitutive activation of multiple survival pathways, resulting in global dysregulation of apoptosis and resistance to activation-induced cell death. We reported previously that nuclear factor kappa B (NF-κB) is a central regulator of the survival network for leukemic LGL...
April 26, 2018: Blood
https://www.readbyqxmd.com/read/29417693/mutations-in-the-signal-transducer-and-activator-of-transcription-family-of-genes-in-cancer
#2
REVIEW
Nahid Shahmarvand, Alexandra Nagy, Jahanbanoo Shahryari, Robert S Ohgami
In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of seven genes, STAT1-4, STAT5A, STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, is important in oncogenesis in both solid and hematopoietic cancers. In the case of hematopoietic neoplasms, STAT3 driver mutations have been described in T-cell large granular lymphocytic (T-LGL) leukemia and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30%-40% of T-LGL leukemia patients...
April 2018: Cancer Science
https://www.readbyqxmd.com/read/29365010/t-cell-large-granular-lymphocytic-leukemia-and-coexisting-b-cell-lymphomas-a-study-from-the-bone-marrow-pathology-group
#3
Tanu Goyal, Beenu Thakral, Sa A Wang, Carlos E Bueso-Ramos, Min Shi, Dragan Jevremovic, William G Morice, Qian-Yun Zhang, Tracy I George, Kathryn K Foucar, Siddharth Bhattacharyya, Adam Bagg, Heesun J Rogers, Juraj Bodo, Lisa Durkin, Eric D Hsi
Objective: T-cell large granular lymphocytic (T-LGL) leukemia is associated with B-cell lymphomas (BCLs), especially small BCLs. We aimed to explore and expand upon its association with BCLs. Methods: We retrospectively studied clinicopathologic features of T-LGL leukemia patients with coexisting BCL from January 2001 to December 2016. Results: Among 432 patients with T-LGL leukemia, 22 (5.1%) had an associated B-cell non-Hodgkin lymphoma...
January 29, 2018: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/29281994/successful-treatment-of-cerebral-aspergillosis-case-report-of-a-patient-with-t-cell-large-granular-lymphocytic-leukemia-t-lgl
#4
Amin T Turki, Jassin Rashidi-Alavijeh, Jan Dürig, Guido Gerken, Peter-Michael Rath, Oliver Witzke
BACKGROUND: Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients...
December 28, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29228628/drug-sensitivity-profiling-identifies-potential-therapies-for-lymphoproliferative-disorders-with-overactive-jak-stat3-signaling
#5
Heikki Kuusanmäki, Olli Dufva, Elina Parri, Arjan J van Adrichem, Hanna Rajala, Muntasir M Majumder, Bhagwan Yadav, Alun Parsons, Wing C Chan, Krister Wennerberg, Satu Mustjoki, Caroline A Heckman
Constitutive JAK/STAT3 signaling contributes to disease progression in many lymphoproliferative disorders. Recent genetic analyses have revealed gain-of-function STAT3 mutations in lymphoid cancers leading to hyperactivation of STAT3, which may represent a potential therapeutic target. Using a functional reporter assay, we screened 306 compounds with selective activity against various target molecules to identify drugs capable of inhibiting the cellular activity of STAT3. Top hits were further validated with additional models including STAT3-mutated natural killer (NK)-cell leukemia/lymphoma cell lines and primary large granular lymphocytic (LGL) leukemia cells to assess their ability to inhibit STAT3 phosphorylation and STAT3 dependent cell viability...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29222254/chronic-neutropenia-in-lgl-leukemia-and-rheumatoid-arthritis
#6
REVIEW
Tal Gazitt, Thomas P Loughran
This section reviews the diagnostic criteria and pathogenesis of large granular lymphocyte (LGL) leukemia. There is a particular focus on the overlap of LGL leukemia and rheumatoid arthritis (Felty's syndrome). Current understanding of the mechanisms of neutropenia in these disorders is discussed. Finally, treatment indications and therapeutic recommendations are outlined.
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29212142/a-guilt-by-association-mutation-network-in-lgl-leukemia
#7
EDITORIAL
Emma I Andersson, Alessandro Coppe, Stefania Bortoluzzi
No abstract text is available yet for this article.
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29058817/dasatinib-cessation-after-deep-molecular-response-exceeding-2-years-and-natural-killer-cell-transition-during-dasatinib-consolidation
#8
MULTICENTER STUDY
Takashi Kumagai, Chiaki Nakaseko, Kaichi Nishiwaki, Chikashi Yoshida, Kazuteru Ohashi, Naoki Takezako, Hina Takano, Yasuji Kouzai, Tadashi Murase, Kosei Matsue, Satoshi Morita, Junichi Sakamoto, Hisashi Wakita, Hisashi Sakamaki, Koiti Inokuchi
Tyrosine kinase inhibitors (TKI) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMR); some patients have successfully discontinued TKI therapy after maintaining DMR for ≥1 year. In this cessation study, we investigated the optimal conditions for dasatinib discontinuation in patients who maintained DMR for ≥2 years. This study included 54 patients with CML who were enrolled in a D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation...
January 2018: Cancer Science
https://www.readbyqxmd.com/read/28977911/stat3-mutation-impacts-biological-and-clinical-features-of-t-lgl-leukemia
#9
Antonella Teramo, Gregorio Barilà, Giulia Calabretto, Chiara Ercolin, Thierry Lamy, Aline Moignet, Mikael Roussel, Cédric Pastoret, Matteo Leoncin, Cristina Gattazzo, Anna Cabrelle, Elisa Boscaro, Sara Teolato, Elisa Pagnin, Tamara Berno, Elena De March, Monica Facco, Francesco Piazza, Livio Trentin, Gianpietro Semenzato, Renato Zambello
STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features. Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8±) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France)...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#10
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28723629/stat3-mutation-impacts-biological-and-clinical-features-of-t-lgl-leukemia
#11
Antonella Teramo, Gregorio Barilà, Giulia Calabretto, Chiara Ercolin, Thierry Lamy, Aline Moignet, Mikael Roussel, Cédric Pastoret, Matteo Leoncin, Cristina Gattazzo, Anna Cabrelle, Elisa Boscaro, Sara Teolato, Elisa Pagnin, Tamara Berno, Elena De March, Monica Facco, Francesco Piazza, Livio Trentin, Gianpietro Semenzato, Renato Zambello
STAT3 mutations have been described in 30-40% of T-large granular lymphocyte (T-LGL) leukemia patients, leading to STAT3 pathway activation. Considering the heterogeneity of the disease and the several immunophenotypes that LGL clone may express, the aim of this work was to evaluate whether STAT3 mutations might be associated with a distinctive LGL immunophenotype and/or might be indicative for specific clinical features.Our series of cases included a pilot cohort of 101 T-LGL leukemia patients (68 CD8+/CD4- and 33 CD4+/CD8±) from Padua Hematology Unit (Italy) and a validation cohort of additional 20 patients from Rennes Hematology Unit (France)...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28717070/clinical-features-pathogenesis-and-treatment-of-large-granular-lymphocyte-leukemias
#12
REVIEW
Kazuo Oshimi
Large granular lymphocytes (LGLs) are large lymphocytes with azurophilic granules in their cytoplasm. LGLs are either natural killer (NK) cells or T lymphocytes. Expansions of the LGLs in the peripheral blood are seen in various conditions, including three clonal disorders: T-cell LGL (T-LGL) leukemia, chronic lymphoproliferative disorders of NK cells (CLPD-NK), and aggressive NK-cell leukemia (ANKL). However, the monoclonal and polyclonal expansion of LGLs has been associated with many other conditions. The present article describes these LGL disorders, with special emphasis on the clinical features, pathogenesis, and treatments of the three above-mentioned clonal disorders...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28454252/multifactorial-neutropenia-in-a-patient-with-acute-promyelocytic-leukemia-and-associated-large-granular-lymphocyte-expansion-a-case-report
#13
Gianluigi Reda, Bruno Fattizzo, Ramona Cassin, Elena Flospergher, Nicola Orofino, Umberto Gianelli, Wilma Barcellini, Agostino Cortelezzi
Neutropenia in the setting of acute hematological malignancies may impact disease prognosis, thus affecting therapy dose intensity. This is often due to chemotherapy-induced aplasia as well as to the disease itself. However, chronic neutropenia deserves further investigation, as the management of reversible concomitant causes may avoid treatment delay. The present study describes a case of an acute promyelocytic leukemia patient with chronic severe neutropenia of multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune activation with anti-platelets and anti-neutrophil antibodies positivity, and the rare association of large granular lymphocyte (LGL) expansion...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28427176/metronomic-regimen-as-an-effective-treatment-for-aggressive-t-lgl-leukemia-with-central-nervous-system-infiltration-clinical-experience-and-review-of-literature
#14
REVIEW
Yun Liu, Lei Fan, Huihui Zhao, Wei Xu, Jianyong Li
A 71-year-old man was diagnosed with T-Large granular lymphocytic (LGL) leukemia, which usually represents a relatively indolent clinical course. While the clinical manifestation of this patient we report herein was aggressive with lasting fever, splenomegaly and hemophagocytic lymphohistiocytosis (HLH). T-cell immunophenotype was CD3+CD4-CD8-CD5-CD7-TCRαβ+. After comprehensive evaluation, an adjusted chemotherapy regimen CEOP (cyclophosphamide, vincristine, etoposide, prednisone) with etoposide, a potential effective regimen for HLH was administrated to the patient...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407008/dysregulated-signaling-proliferation-and-apoptosis-impact-on-the-pathogenesis-of-tcr%C3%AE-%C3%AE-t-cell-large-granular-lymphocyte-leukemia
#15
Martine J Kallemeijn, Dick de Ridder, Joyce Schilperoord-Vermeulen, Michèle Y van der Klift, Yorick Sandberg, Jacques J M van Dongen, Anton W Langerak
TCRγδ+ T-LGL leukemia is a rare form of chronic mature T cell disorders in elderly, which is generally characterized by a persistently enlarged CD3+CD57+TCRγδ+ large granular lymphocyte population in the peripheral blood with a monoclonal phenotype. Clinically, the disease is heterogeneous, most patients being largely asymptomatic, although neutropenia, fatigue and B symptoms and underlying diseases such as autoimmune diseases or malignancies are also often observed. The etiology of TCRγδ+ T-LGL proliferations is largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28401952/correlations-in-the-degeneracy-of-structurally-controllable-topologies-for-networks
#16
Colin Campbell, Steven Aucott, Justin Ruths, Derek Ruths, Katriona Shea, Réka Albert
Many dynamic systems display complex emergent phenomena. By directly controlling a subset of system components (nodes) via external intervention it is possible to indirectly control every other component in the system. When the system is linear or can be approximated sufficiently well by a linear model, methods exist to identify the number and connectivity of a minimum set of external inputs (constituting a so-called minimal control topology, or MCT). In general, many MCTs exist for a given network; here we characterize a broad ensemble of empirical networks in terms of the fraction of nodes and edges that are always, sometimes, or never a part of an MCT...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28128670/large-granular-lymphocytic-leukemia-current-diagnostic-and-therapeutic-approaches-and-novel-treatment-options
#17
REVIEW
Estella Matutes
Large granular lymphocytic leukemia (LGLL) is a low grade lymphoproliferative disorder characterized by the clonal proliferation of large granular lymphocytes (LGL) and recognised by the WHO. The diagnosis and management of these patients is challenging due to the limited information from prospective studies. Guidelines for front-line therapy have not been established. The prognosis is favourable with median overall survivals greater than 10 years. Areas covered: This manuscript is a review of the clinical features, diagnosis, pathogenesis and, in particular, the various available therapeutic options for this rare lymphoid leukemia...
March 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28115367/lgl-leukemia-from-pathogenesis-to-treatment
#18
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/27932186/late-graft-rejection-in-association-with-t-large-granular-lymphocyte-expansion-of-recipient-origin-after-human-leukocyte-antigen-haploidentical-stem-cell-transplantation-a-case-report
#19
N Nakagawa, H Yamazaki, G Aoki, Y Kondo, S Nakao
BACKGROUND: Large granular lymphocyte (LGL) expansion occasionally occurs after allogeneic stem cell transplantation (allo-SCT), and is thought to be a good prognostic sign that is associated with a lower relapse rate. However, there have been no reports of late graft failure (LGF) due to graft rejection in association with oligoclonal LGL expansion. We herein report a case of LGF associated with the transient expansion of recipient-derived T-LGL after allo-SCT. CASE REPORT: A 65-year-old man underwent peripheral blood stem cell transplantation (PBSCT) from his human leukocyte antigen (HLA)-haploidentical son for the treatment of acute myeloid leukemia, which had evolved from a myelodysplastic syndrome (MDS)...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27755009/distinguishing-between-hepatosplenic-t-cell-lymphoma-and-%C3%AE-%C3%AE-t-cell-large-granular-lymphocytic-leukemia-a-clinicopathologic-immunophenotypic-and-molecular-analysis
#20
Mariko Yabe, L Jeffrey Medeiros, Sa A Wang, Guilin Tang, Carlos E Bueso-Ramos, Jeffrey L Jorgensen, Govind Bhagat, Weina Chen, Shaoying Li, Ken H Young, Roberto N Miranda
Hepatosplenic T-cell lymphoma (HSTCL) is a rare, aggressive T-cell lymphoma that can be challenging to diagnose. In particular, distinguishing HSTCL from T-cell large granular lymphocytic (T-LGL) leukemia of γδ T-cell receptor (TCR) type is difficult without examination of a splenectomy specimen. In this study, we systematically assessed a series of HSTCL cases for findings reported in the literature as supporting or not supporting the diagnosis of HSTCL. We also compared HSTCL with a group of cases of T-LGL of γδ TCR type...
January 2017: American Journal of Surgical Pathology
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