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T cell leukemia

Benjamin Neveu, Maxime Caron, Karine Lagacé, Chantal Richer, Daniel Sinnett
Genetic alterations in the transcriptional repressor ETV6 are associated with hematological malignancies. Notably, the t(12;21) translocation leading to an ETV6-AML1 fusion gene is the most common genetic alteration found in childhood acute lymphoblastic leukemia. Moreover, most of these patients also lack ETV6 expression, suggesting a tumor suppressor function. To gain insights on ETV6 DNA-binding specificity and genome wide transcriptional regulation capacities, we performed chromatin immunoprecipitation experiments coupled to deep sequencing in a t(12;21)-positive pre-B leukemic cell line...
October 19, 2018: Scientific Reports
Wasil Jastaniah, Mohamed Bayoumy, Abdulrahman Alsultan, Saad Al Daama, Walid Ballourah, Faisal Al-Anzi, Omar Al Shareef, Reem Al Sudairy, Mohammed Burhan Abrar, Ibrahim Al Ghemlas
BACKGROUND: The outcome of childhood acute myeloid leukemia (AML) in first relapse (rAML) remains poor. Reported overall survival (OS) rates vary between high-income developed countries and those with fewer resources. The OS of rAML in high-income developing countries (HIDCs) has not been reported. PATIENTS AND MATERIALS: A multicenter study was performed in an HIDC. The outcome of patients with relapsed non-M3/non-Down syndrome AML was evaluated. Three-year OS was computed using the Kaplan-Meier method, and predictors of OS were analyzed using a Cox proportional hazards model...
September 12, 2018: Clinical Lymphoma, Myeloma & Leukemia
Jose L Lepe-Zuniga, Virginia Ramirez-Nova
Childhood Lymphoblastic leukemia's (ALL) early mortality (EM) is an undesirable treatment outcome for a disease for which >90% long term success is achievable. In the Western world EM constitutes no >3%; yet, in Chiapas, Mexico, remains around 15%. With the objective of improving on EM, we determined associated elements in 28 ALL who died within 60 days of arriving at Hospital de Especialidades Pediátricas in Chiapas (HEP), by comparing them to those in 84 controls who lived beyond the first 90 days...
October 18, 2018: Journal of Pediatric Hematology/oncology
Nicole Weiler, Erick F Mayer, Viktoryia Kazlouskaya, Oluwatoyin F Bamgbola, Natalie Banniettis, Edward Heilman, Sharon A Glick
Infective dermatitis (ID) associated with Human T-cell leukemia virus type-1 (HTLV-1) is a rare form of severe superinfected eczema seen mostly in the Caribbean islands and Latin America. Although rapid response to antibiotic treatment is observed, patients should be monitored for development of complications associated with this retroviral infection, including T-cell leukemia/lymphoma (ATLL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Infective dermatitis is rarely seen in the United States and therefore may be under-recognized by physicians unfamiliar with this condition...
October 18, 2018: Pediatric Dermatology
Toru Kawakami, Nodoka Sekiguchi, Jun Kobayashi, Tatsuya Imi, Kazuyuki Matsuda, Taku Yamane, Sayaka Nishina, Yasushi Senoo, Hitoshi Sakai, Toshiro Ito, Tomonobu Koizumi, Makoto Hirokawa, Shinji Nakao, Hideyuki Nakazawa, Fumihiro Ishida
Dysregulation of T-cell-mediated immunity is responsible for acquired pure red cell aplasia (PRCA). Although STAT3 mutations are frequently detected in patients with T-cell large granular lymphocytic leukemia (T-LGLL), which is often complicated by PRCA and which is also reported to be associated with acquired aplastic anemia (AA) and myelodysplastic syndrome (MDS), whether STAT3 -mutated T cells are involved in the pathophysiology of PRCA and other types of bone marrow failure remains unknown. We performed STAT3 mutation analyses of the peripheral blood mononuclear cells from PRCA patients (n = 42), AA (n = 54), AA-paroxysmal nocturnal hemoglobinuria (AA-PNH; n = 7), and MDS (n = 21) using an allele-specific polymerase chain reaction and amplicon sequencing...
October 23, 2018: Blood Advances
Razavi Hashemi M, Vahabpour R, Ranji N, Sanati Mh, Mapar M, Sadat Sm
BACKGROUND: Acute T Cell Leukemia (ALL) is an aggressive and prevalent human malignancy. Chemotherapy is the most frequent therapeutic strategy; however, cytotoxicity and recurrence of cancer are the main concerns. The discovery of microRNA (miRNA) drew the attention of scientists who were working on targeted cancer therapy to use the potential of gene regulation by using this small RNAs. METHODS: miRanda, TargetScan, miRDB databases, and miRWalk software were applied to find probable miRNAs targeting 3'UTR of JAK1, STAT3, SOCS6, AKT1, APAF, BID, and Caspase9 mRNA...
October 1, 2018: Clinical Laboratory
Jing-Wen Zhang, Yun-Xin Zeng, Jia-Yin Liang, Ling Zhang, Xin-Bao Zhao, Jian-Hua Pan, Ruo-Zhi Xiao
BACKGROUND: We herein report a fatal case of fulminant septicemia caused by Bacillus cereus in a 49-year-old female with T-cell acute lymphoblastic leukemia receiving chemotherapy. METHODS: Her two blood culture sets were positive for Gram-positive, rod-shaped bacterium. Bacillus cereus was identified by high-throughput MALDI-TOF mass spectrometry and 16S ribosomal RNA gene sequencing. RESULTS: The patient died within 12 hours from the onset of B cereus infection...
October 1, 2018: Clinical Laboratory
Eman Mosaad Zaki, Asmaa Mohamed Zahran, Alshimaa Abdelazeem Metwaly, Rania Hafez, Safinaz Hussein, Abdallah Elaiw Mohammed
OBJECTIVE/BACKGROUND: Chronic lymphocytic leukemia is one of the commonest leukemias affecting adults. CD39 inhibits T-cell and NK cell responses by hydrolyzing adenosine triphosphate and adenosine diphosphate, suppressing the immune system. We investigated expression of CD39 on CD4+ T Lymphocytes in chronic lymphocytic leukemia (CLL) patients and its relationship with deletion 6q, its association with disease stage and survival. METHODS: Thirty CLL patients and 20 matched controls were included in the study...
October 11, 2018: Hematology/oncology and Stem Cell Therapy
Genjie Wang, Ying Tian, Qingzhu Hu, Xichun Xiao, Shuxia Chen
The promyelocytic leukemia (PML)/retinoic acid receptor-alpha (RARα) onco-fusion protein that is generated from t(15;17) chromosome translocation is crucial for the leukemogenesis of acute promyelocytic leukemia (APL) and is well documented as a transcriptional repressor. To understand the relationship between PML/RARα and the oncogene in the development of APL, we investigate the regulation mechanism of PML/RARα to MYB proto-oncogene and the role of this regulation on the proliferation and differentiation of APL cells...
October 18, 2018: Journal of Cellular Biochemistry
Houfang Sun, Sheng Wei, Lili Yang
OBJECTIVES: Large granular lymphocyte (LGL) leukemia is a rare type of lymphoproliferative disease caused by clonal antigenic stimulation of T cells and natural killer (NK) cells. METHODS: In this review, we focus on the current knowledge of the immunological dysfunctions associated with LGL leukemia and the associated disorders coexistent with this disease. Novel therapeutic options targeting known molecular mechanisms are also discussed. RESULTS AND DISCUSSION: The pathogenesis of LGL leukemia involves the accumulation of gene mutations, dysregulated signaling pathways and immunological dysfunction...
October 18, 2018: Hematology (Amsterdam, Netherlands)
T Jiang, J Chen, X Huang, Y Li, L Zhong
Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) is the most fatal leukemia due to the BCR/ABL fusion protein. This fusion protein could induce the interleukin 6 (IL-6) expression in leukemia stem cells (LSCs), which sustain the stemness by binding IL-6R and activating Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. IL-6R was one of the targets of miR-451a, which was downregulated in LSCs by BCR/ABL. We aimed to investigate the relationship between miR-451a, IL-6R, and BCR/ABL in Ph+ ALL and create a strategy to treat this disease...
September 4, 2018: Neoplasma
Catarina Simões, Isabel Silva, Anabela Carvalho, Sandra Silva, Susana Santos, Gilberto Marques, André Ribeiro, Adriana Roque, José Carda, A B Sarmento-Ribeiro, Maria do Rosário Domingues, Letícia Ribeiro, Artur Paiva
BACKGROUND: Vδ1+ T cells, a subset of γδ T cells, are responsible for innate-like immune responses. Recently, an anti-tumor function mediated by MHC-unrestricted recognition of lipid and stress molecules, has also been described in these cells. This study aimed to quantify and phenotypically characterize circulating Vδ1+ T cells in B cell Chronic Lymphocytic Leukemia (CLL) and Monoclonal B cell lymphocytosis (MBL). METHODS: This study enrolled 58 individuals distributed in five groups: Binet B and C CLL (n = 9), Binet A CLL (n = 26), High count-MBL (n = 10), Low count-MBL (n = 5), and a control group (n = 8)...
October 17, 2018: Cytometry. Part B, Clinical Cytometry
Anurag Kulkarni, Graham P Taylor, Robert J Klose, Christopher J Schofield, Charles Rm Bangham
It is not understood how the human T cell leukemia virus human T-lymphotropic virus-1 (HTLV-1), a retrovirus, regulates the in vivo balance between transcriptional latency and reactivation. The HTLV-1 proviral plus-strand is typically transcriptionally silent in freshly isolated peripheral blood mononuclear cells from infected individuals, but after short-term ex vivo culture, there is a strong, spontaneous burst of proviral plus-strand transcription. Here, we demonstrate that proviral reactivation in freshly isolated, naturally infected primary CD4+ T cells has 3 key attributes characteristic of an immediate-early gene...
October 18, 2018: JCI Insight
Greg P Coffey, Greg P Coffey, Andreas Betz, Jiajia Feng, Anjali Pandey, Matt Birrell, Janet M Leeds, Kenneth Der, Sabah Kadri, Pin Lu, Jeremy P Segal, Y Lynn Wang, Glenn Michelson, John T Curnutte, Pamela B Conley
PURPOSE: Preclinical studies suggest SYK and JAK contribute to tumor intrinsic and microenvironment-derived survival signals. The pharmacodynamics of cerdulatinib, a dual SYK/JAK inhibitor, and associations with tumor response were investigated. EXPERIMENTAL DESIGN: In a phase I dose-escalation study in adults with relapsed/refractory B-cell malignancies, cerdulatinib was administered orally to sequential dose-escalation cohorts using once-daily or twice-daily schedules...
October 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Roberto Mina, Nisha S Joseph, Jonathan L Kaufman, Vikas A Gupta, Leonard T Heffner, Craig C Hofmeister, Lawrence H Boise, Madhav V Dhodapkar, Charise Gleason, Ajay K Nooka, Sagar Lonial
BACKGROUND: Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder characterized by circulating plasma cells and a poor prognosis. Although patients who have pPCL benefit from the use of stem cell transplantation (SCT) and novel agents, their prognosis remains inferior to that of patients who have myeloma. METHODS: This was a retrospective analysis of 38 consecutive patients with pPCL who were diagnosed between October 2005 and July 2016 and were registered in the Winship Cancer Institute of Emory University database...
October 17, 2018: Cancer
Lindsey Hathaway, Jeremy Michael Sen, Michael Keng
Relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is associated with a poor prognosis in both children and adults. Traditionally, there were limited options for salvage therapy, which consisted mostly of conventional chemotherapy. However, in the past 5 years, novel agents have changed our treatment strategies in this population. Blinatumomab, a bispecific CD19 directed CD3 T-cell engager, has shown to be effective in both minimal residual disease and R/R B-cell ALL. In R/R B-cell ALL, blinatumomab was associated with an improved median overall survival of 7...
2018: Patient related Outcome Measures
Wei Zhang, Kimberly R Jordan, Brian Schulte, Enkhtsetseg Purev
Background: Chimeric antigen receptor (CAR) T-cell therapy is highly effective for treating acute lymphoblastic leukemia and non-Hodgkin's lymphoma with high rate complete responses. However, the broad clinical application of CAR T-cell therapy has been challenging, largely due to the lack of widespread ability to produce and high cost of CAR T-cell products using traditional methods of production. Automated cell processing in a closed system has emerged as a potential method to increase the feasibility of producing CAR T cells locally at academic centers due to its minimal reliance on experienced labor, thereby making the process less expensive and more consistent than traditional methods of production...
2018: Drug Design, Development and Therapy
Hexiu Su, Juncheng Hu, Liang Huang, Yang Yang, Morgan Thenoz, Anna Kuchmiy, Yufeng Hu, Peng Li, Hui Feng, Yu Zhou, Tom Taghon, Pieter Van Vlierberghe, Guoliang Qing, Zhichao Chen, Hudan Liu
T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with complicated heterogeneity. Although expression profiling reveals common elevated genes in distinct T-ALL subtypes, little is known about their functional role(s) and regulatory mechanism(s). We here show that SHQ1, an H/ACA snoRNP assembly factor involved in snRNA pseudouridylation, is highly expressed in T-ALL. Mechanistically, oncogenic NOTCH1 directly binds to the SHQ1 promoter and activates its transcription. SHQ1 depletion induces T-ALL cell death in vitro and prolongs animal survival in murine T-ALL models...
October 15, 2018: Nature Communications
Xia Xiao, Xiaoyuan He, Qing Li, Huan Zhang, Juanxia Meng, Yanyu Jiang, Qi Deng, Mingfeng Zhao
BACKGROUND: Tumor immunotherapy with chimeric antigen receptor T cells (CAR-T) is a promising new treatment for B-cell malignancies and has produced exciting results. However, cytokine release syndrome (CRS) is the most significant toxicity associated with this treatment and can be life-threatening. CASE PRESENTATION: A 23-year-old male patient had been diagnosed with relapsed and refractory B-cell acute lymphocytic leukemia. The patient was recruited into our CAR-T clinical trial, and 1×106 /kg of engineered anti-CD19 CAR-T cells was administered...
October 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Stephanie M Davis, Lisa A Collier, Edric D Winford, Christopher C Leonardo, Craig T Ajmo, Elspeth A Foran, Timothy J Kopper, John C Gensel, Keith R Pennypacker
BACKGROUND: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke...
October 15, 2018: Journal of Neuroinflammation
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