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Large granular lymphocytic leukemia

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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
#1
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
#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 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
#3
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
#4
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 20, 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
#5
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
#6
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...
December 26, 2017: 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
#7
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
#8
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
#9
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-the-felty-syndrome-an-implication-for-a-common-pathogenesis-with-large-granular-lymphocyte-leukemia
#10
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. We now aimed to study whether these mutations can also be detected in Felty syndrome, which would imply for a common pathogenic mechanism between these two disease entities. We collected samples and clinical information from 14 Felty syndrome patients who were monitored at the rheumatology outpatient clinic for Felty syndrome...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29217782/rational-management-approach-to-pure-red-cell-aplasia
#11
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 without rationally established standard therapies. Most cases are idiopathic; a subset is antibody-mediated. There is overlap between idiopathic cases and those with T-large granular lymphocytic leukemia, hypogammaglobulinemia, and low-grade lymphomas. In all these, 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 to propose diagnostic and therapeutic algorithms that may help guide management of prospective patients...
December 7, 2017: Haematologica
https://www.readbyqxmd.com/read/29204452/recurrent-lactobacillus-bacteremia-in-a-patient-with-leukemia
#12
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-nk-cell-transition-during-dasatinib-consolidation
#13
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 (TKIs) improve the prognosis of patients with chronic myelogenous leukemia (CML) by inducing substantial deep molecular responses (DMRs); some patients could successfully discontinue 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 D-STOP multicenter prospective trial, had achieved DMR, and had discontinued dasatinib after 2-year consolidation...
October 23, 2017: Cancer Science
https://www.readbyqxmd.com/read/28977911/stat3-mutation-impacts-biological-and-clinical-features-of-t-lgl-leukemia
#14
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
#15
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
#16
M Paige Kulling, C Kristine Olson, L Thomas Olson, E Cait Hamele, N Kathryn Carter, J David Feith, P Thomas 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)...
July 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28723629/stat3-mutation-impacts-biological-and-clinical-features-of-t-lgl-leukemia
#17
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
#18
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/28633612/clinical-features-and-treatment-outcomes-in-large-granular-lymphocytic-leukemia-lgll
#19
Srinivasa R Sanikommu, Michael J Clemente, Peter Chomczynski, Manuel G Afable, Andres Jerez, Swapna Thota, Bhumika Patel, Cassandra Hirsch, Aziz Nazha, John Desamito, Alan Lichtin, Brad Pohlman, Mikkael A Sekeres, Tomas Radivoyevitch, Jaroslaw P Maciejewski
Large granular lymphocytic leukemia (LGLL) represents a clonal/oligoclonal lymphoproliferation of cytotoxic T and natural killer cells often associated with STAT3 mutations. When symptomatic, due to mostly anemia and neutropenia, therapy choices are often empirically-based, because only few clinical trials and systematic studies have been performed. Incorporating new molecular and flow cytometry parameters, we identified 204 patients fulfilling uniform criteria for LGLL diagnoses and analyzed clinical course with median follow-up of 36 months, including responses to treatments...
February 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28623913/aggressive-natural-killer-cell-leukemia-or-extranodal-nk-t-cell-lymphoma-a-case-with-nasal-involvement
#20
Xiaoke Jin, Youhai Xu, Jun Zhang, Guangxi Li, Dongping Huang, Yuqiong Yang, Hesheng He
BACKGROUND: Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis. CASE PRESENTATION: A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction...
June 17, 2017: Diagnostic Pathology
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