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LGL Leukemia

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https://www.readbyqxmd.com/read/29058817/dasatinib-cessation-after-deep-molecular-response-exceeding-2-years-and-nk-cell-transition-during-dasatinib-consolidation
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27715403/vitamin-d-decreases-stat-phosphorylation-and-inflammatory-cytokine-output-in-t-lgl-leukemia
#14
Kristine C Olson, Paige M Kulling, Thomas L Olson, Su-Fern Tan, Rebecca J Rainbow, David J Feith, Thomas P Loughran
Large granular lymphocyte leukemia (LGLL) is a rare incurable chronic disease typically characterized by clonal expansion of CD3+ cytotoxic T-cells. Two signal transducer and activator of transcription factors, STAT1 and STAT3, are constitutively active in T-LGLL. Disruption of this activation induces apoptosis in T-LGLL cells. Therefore, considerable efforts are focused on developing treatments that inhibit STAT activation. Calcitriol, the active form of vitamin D, has been shown to decrease STAT1 and STAT3 phosphorylation in cancer cell lines and autoimmune disease mouse models...
May 4, 2017: Cancer Biology & Therapy
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
#15
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/27640075/single-center-series-of-bone-marrow-biopsy-defined-large-granular-lymphocyte-leukemia-high-rates-of-sustained-response-to-oral-methotrexate
#16
Talha Munir, Mark J Bishton, Ian Carter, Andrew McMillan, Simon O'Connor, Vishakha Sovani, Andrew P Haynes, Christopher P Fox
INTRODUCTION: Large granular lymphocyte (LGL) leukemia is a rare chronic lymphoproliferative disorder, with few large series reported to date. Series using stringent diagnostic criteria incorporating bone marrow biopsy (BMB), immunophenotyping, and T-cell receptor rearrangements are even scarcer. PATIENTS AND METHODS: The present study was a single-center series of 39 patients with LGL leukemia diagnosed using immunohistochemical analysis of BMB samples and flow cytometric and molecular data...
December 2016: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/27496109/donor-derived-t-cell-large-granular-lymphocytic-leukemia-in-a-patient-with-peripheral-t-cell-lymphoma
#17
Juliana E Hidalgo Lopez, Mariko Yabe, Adrian A Carballo-Zarate, Sa A Wang, Jeffrey L Jorgensen, Sairah Ahmed, John Lee, Shaoying Li, Ellen Schlette, Timothy McDonnell, Roberto N Miranda, L Jeffrey Medeiros, Carlos E Bueso-Ramos, C Cameron Yin
T-cell large granular lymphocytic (T-LGL) leukemia after hematopoietic stem cell transplantation (SCT) is rare and its natural history and clinical outcome have not been well described. We report the clinical, morphologic, immunophenotypic, and molecular features of a case of donor-derived T-LGL leukemia in a 16-year-old man who received allogeneic SCT for peripheral T-cell lymphoma not otherwise specified (PTCL-NOS). The patient presented with persistent neutropenia and splenomegaly 9 months after SCT when the chimerism study showed a 100% donor pattern...
August 2016: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/27494824/a-population-based-study-of-large-granular-lymphocyte-leukemia
#18
M V Shah, C C Hook, T G Call, R S Go
Large granular lymphocyte (LGL) leukemia is a lymphoproliferative disorder of cytotoxic cells. T-cell LGL (T-LGL) leukemia is characterized by accumulation of cytotoxic T cells in blood and infiltration of the bone marrow, liver or spleen. Population-based studies have not been reported in LGL leukemia. We present clinical characteristics, natural history and risk factors for poor survival in patients with LGL leukemia using the Surveillance, Epidemiology, and End Results Program (SEER) and the United States National Cancer Data Base (NCDB)...
August 5, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27278595/the-legacy-of-the-f344-rat-as-a-cancer-bioassay-model-a-retrospective-summary-of-three-common-f344-rat-neoplasms
#19
REVIEW
Robert R Maronpot, Abraham Nyska, Jennifer E Foreman, Yuval Ramot
The Fischer 344 (F344) rat was used by the National Toxicology Program (NTP) for over 5 decades for toxicity and carcinogenicity studies. However, in 2006, the NTP decided to switch to a different rat stock due largely to high background control incidences of Leydig cell tumors (LCTs) and mononuclear cell leukemia (MNCL), also known as large granular lymphocytic (LGL) leukemia. In the current review, we aim (1) to provide a summary of NTP bioassays with treatment-associated effects involving MNCL and LCTs in addition to male F344-specific tunica vaginalis mesothelioma (TVM); (2) to describe important pathobiological differences between these F344 rat tumor responses and similar target tissue-tumor response in humans; and (3) to present the NTP reasons for switching away from the F344 rat...
September 2016: Critical Reviews in Toxicology
https://www.readbyqxmd.com/read/27064362/cell-size-variations-of-large-granular-lymphocyte-leukemia-implication-of-a-small-cell-subtype-of-granular-lymphocyte-leukemia-with-stat3-mutations
#20
Takahiro Tanahashi, Nodoka Sekiguchi, Kazuyuki Matsuda, Yuka Takezawa, Toshiro Ito, Hikaru Kobayashi, Naoaki Ichikawa, Sayaka Nishina, Noriko Senoo, Hitoshi Sakai, Hideyuki Nakazawa, Fumihiro Ishida
Large granular lymphocyte leukemia (LGL-L) has been morphologically defined 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 26 LGL-L patients in order to elucidate relationships with current classifications and molecular backgrounds. LGL-L cells were mostly indistinguishable from normal LGL...
June 2016: Leukemia Research
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