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Large granular lymphocyte leukemia

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https://www.readbyqxmd.com/read/29607828/t-cell-large-granular-lymphocytic-leukemia-with-pulmonary-hypertension
#1
Sidra Khalid, Hamed Daw, Miriam Jacob, Megan Nakashima
T cell large granular lymphocytic leukemia is a hematological disorder which is characterized by the proliferation of CD 3+ cytotoxic T cells. We present a case about a patient who was diagnosed with T cell large granular lymphocytic leukemia and then developed pulmonary hypertension. He was treated for his leukemia with methotrexate and simultaneously treated for his pulmonary hypertension with selexipag and ambrisentan. As his leukemia improved, we also noticed an improvement in his pulmonary hypertension from a NYHA class IV to class I...
January 2018: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/29559980/next-generation-sequencing-analysis-of-the-human-tcr%C3%AE-%C3%AE-t-cell-repertoire-reveals-shifts-in-v%C3%AE-and-v%C3%AE-usage-in-memory-populations-upon-aging
#2
Martine J Kallemeijn, François G Kavelaars, Michèle Y van der Klift, Ingrid L M Wolvers-Tettero, Peter J M Valk, Jacques J M van Dongen, Anton W Langerak
Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to autoimmunity and cancer development at older age. Even though TCRαβ+ and TCRγδ+ T-cells follow similar paths of development involving V(D)J-recombination of TCR genes in the thymus, TCRγδ+ T-cells tend to be more subjected to peripheral rather than central selection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29474442/dysregulation-of-the-ifn-%C3%AE-stat1-signaling-pathway-in-a-cell-line-model-of-large-granular-lymphocyte-leukemia
#3
Paige M Kulling, Kristine C Olson, Cait E Hamele, Mariella F Toro, Su-Fern Tan, David J Feith, Thomas P Loughran
T cell large granular lymphocyte leukemia (T-LGLL) is a rare incurable disease that is characterized by defective apoptosis of cytotoxic CD8+ T cells. Chronic activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway is a hallmark of T-LGLL. One manifestation is the constitutive phosphorylation of tyrosine 701 of STAT1 (p-STAT1). T-LGLL patients also exhibit elevated serum levels of the STAT1 activator, interferon-γ (IFN-γ), thus contributing to an inflammatory environment...
2018: PloS One
https://www.readbyqxmd.com/read/29473430/lymphomatoid-granulomatosis-and-large-granular-lymphocyte-leukemia-a-rare-association-of-two-lymphoproliferative-disorders
#4
Giulia De Luca, Stefania Trasarti, Luisa Bizzoni, Ilaria Del Giudice, Irene Della Starza, Maria Stefania De Propris, Giuseppe Gentile, Francesca Mancini, Sara Mantovani, Luigi Petrucci, Valentina Tabanelli, Anna Guarini, Marco Vignetti, Robin Foà
No abstract text is available yet for this article.
February 23, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29435021/long-lasting-memory-of-cellular-immunity-in-a-chronic-myeloid-leukemia-patient-maintains-molecular-response-5-after-cessation-of-dasatinib
#5
Tatsuro Jo, Kazuhiro Noguchi, Shizuka Hayashi, Sadaharu Irie, Risa Hayase, Haruna Shioya, Youhei Kaneko, Kensuke Horio, Jun Taguchi
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29417693/mutations-in-the-stat-family-of-genes-in-cancer
#6
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 six 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, has been shown to be 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 leukemia (T-LGL) and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30-40% of T-LGL patients...
February 8, 2018: Cancer Science
https://www.readbyqxmd.com/read/29416058/divergent-roles-for-antigenic-drive-in-the-aetiology-of-primary-versus-dasatinib-associated-cd8-tcr-v%C3%AE-expansions
#7
Anna Lissina, James E McLaren, Mette Ilander, Emma I Andersson, Catherine S Lewis, Mathew Clement, Andrew Herman, Kristin Ladell, Sian Llewellyn-Lacey, Kelly L Miners, Emma Gostick, J Joseph Melenhorst, A John Barrett, David A Price, Satu Mustjoki, Linda Wooldridge
CD8+ T-cell expansions are the primary manifestation of T-cell large granular lymphocytic leukemia (T-LGLL), which is frequently accompanied by neutropenia and rheumatoid arthritis, and also occur as a secondary phenomenon in leukemia patients treated with dasatinib, notably in association with various drug-induced side-effects. However, the mechanisms that underlie the genesis and maintenance of expanded CD8+ T-cell receptor (TCR)-Vβ+ populations in these patient groups have yet to be fully defined. In this study, we performed a comprehensive phenotypic and clonotypic assessment of expanded (TCR-Vβ+) and residual (TCR-Vβ-) CD8+ T-cell populations in T-LGLL and dasatinib-treated chronic myelogenous leukemia (CML) patients...
February 7, 2018: Scientific Reports
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
#8
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/29296824/systematic-stat3-sequencing-in-patients-with-unexplained-cytopenias-identifies-unsuspected-large-granular-lymphocytic-leukemia
#9
Elizabeth A Morgan, Mark N Lee, Daniel J DeAngelo, David P Steensma, Richard M Stone, Frank C Kuo, Jon C Aster, Christopher J Gibson, R Coleman Lindsley
No abstract text is available yet for this article.
September 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29288042/stat3-mutation-and-its-clinical-and-histopathologic-correlation-in-t-cell-large-granular-lymphocytic-leukemia
#10
Min Shi, Rong He, Andrew L Feldman, David S Viswanatha, Dragan Jevremovic, Dong Chen, William G Morice
Although T-cell large granular lymphocytic leukemia (T-LGLL) is a clinically indolent disorder, patients with moderate to severe cytopenia require therapeutic intervention. The recent discovery of STAT3 mutations has shed light on the genetic basis of T-LGLL pathogenesis. However, the association of STAT3 mutational status with patients' clinical, histopathologic, and other laboratory features has not been thoroughly evaluated in T-LGLL. In this study, STAT3 mutations were identified in 18 of 36 patients with T-LGLL (50%), including Y640F (12/18, 66...
March 2018: Human 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
#11
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
#12
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
#13
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/29217783/somatic-stat3-mutations-in-felty-syndrome-an-implication-for-a-common-pathogenesis-with-large-granular-lymphocyte-leukemia
#14
Paula Savola, Oscar Brück, Thomas Olson, Tiina Kelkka, Markku J Kauppi, Panu E Kovanen, Soili Kytölä, Tuulikki Sokka-Isler, Thomas P Loughran, Marjatta Leirisalo-Repo, Satu Mustjoki
Felty syndrome is a rare disease defined by neutropenia, splenomegaly, and rheumatoid arthritis. Sometimes the differential diagnosis between Felty syndrome and large granular lymphocyte leukemia is problematic. Recently, somatic STAT3 and STAT5B mutations were discovered in 30-40% of patients with large granular lymphocyte leukemia. Herein, we aimed to study whether these mutations can also be detected in Felty syndrome, which would imply the existence of a common pathogenic mechanism between these two disease entities...
February 2018: Haematologica
https://www.readbyqxmd.com/read/29217782/rational-management-approach-to-pure-red-cell-aplasia
#15
Suresh Kumar Balasubramanian, Meena Sadaps, Swapna Thota, Mai Aly, Bartlomiej P Przychodzen, Cassandra M Hirsch, Valeria Visconte, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Pure red cell aplasia is an orphan disease, and as such lacks rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-cell large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In each of the aforementioned, the pathogenetic mechanisms may involve autoreactive cytotoxic responses. We selected 62 uniformly diagnosed pure red cell aplasia patients and analyzed their pathophysiologic features and responsiveness to rationally applied first-line and salvage therapies in order to propose diagnostic and therapeutic algorithms that may be helpful in guiding the management of prospective patients, 52% of whom were idiopathic, while the others involved large granular lymphocytic leukemia, thymoma, and B-cell dyscrasia...
February 2018: Haematologica
https://www.readbyqxmd.com/read/29204452/recurrent-lactobacillus-bacteremia-in-a-patient-with-leukemia
#16
Paurush Ambesh, Sarah Stroud, Eva Franzova, Joseph Gotesman, Kavita Sharma, Lawrence Wolf, Stephan Kamholz
Lactobacillus species are a commensal flora of the human gastrointestinal and the female genitourinary tract. Lactobacilli especially the rhamnosus species, are common components of commercial probiotics. They are rarely associated with pathology in immunocompetent people, but they have been known to cause dental caries, bacteremia, and endocarditis in patients with suppressed immune function. Cases of Lactobacillus bacteremia have been reported in patients with acute myeloid leukemia, large granular lymphocytic leukemia, and in transplant recipients...
October 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29058817/dasatinib-cessation-after-deep-molecular-response-exceeding-2-years-and-natural-killer-cell-transition-during-dasatinib-consolidation
#17
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
#18
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
#19
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/28736298/calcitriol-mediated-reduction-in-ifn-%C3%AE-output-in-t-cell-large-granular-lymphocytic-leukemia-requires-vitamin-d-receptor-upregulation
#20
Paige M Kulling, Kristine C Olson, Thomas L Olson, Cait E Hamele, Kathryn N Carter, David J Feith, Thomas P Loughran
Constitutively activated STAT1 and elevated IFN-γ are both characteristic of T cell large granular lymphocytic leukemia (T-LGLL), a rare incurable leukemia with clonal expansion of cytotoxic T cells due to defective apoptosis. Interferon gamma (IFN-γ) is an inflammatory cytokine that correlates with worse progression and symptomology in multiple autoimmune diseases and cancers. In canonical IFN-γ-STAT1 signaling, IFN-γ activates STAT1, a transcription factor, via phosphorylation of tyrosine residue 701 (p-STAT1)...
March 2018: Journal of Steroid Biochemistry and Molecular Biology
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